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Volume 96-B, Issue SUPP_11 July 2014 8th Combined Meeting Of Orthopaedic Research Societies (CORS)

B. Gao L. Angibaud

Summary Statement

Femorotibial constraint is a key property of a total knee arthroplasty (TKA) prosthesis and should reflect the intended function of the device. With a validated simulation methodology, this study evaluated the constraint of two TKA prostheses designed for different intentions.

Introduction

TKA prostheses are semi-constrained artificial joints. Femorotibial constraint level is a major property of a prosthesis and should be designed to match the device's intended function. Cruciate Retaining (CR) prostheses are usually indicated for patients with a functioning posterior cruciate ligament (PCL). For patients without a fully functioning PCL, CR-Constrained (CRC) prostheses with additional built-in constraint may be indicated. A CRC prosthesis usually consists of a CR femoral component and a tibial insert which has a more conforming sagittal profile to offer an increased femorotibial constraint. This study evaluated the anterior-posterior (AP) constraint behavior of two lines of prostheses (CR and CRC) from a same TKA product family. Using a validated computer simulation approach, multiple sizes of each product line were evaluated.


B. Gao L. Angibaud

Summary Statement

The constraint behavior of total knee arthroplasty (TKA) prosthesis usually has to be physically tested. This study presents a computer simulation model using finite element analysis (FEA) and demonstrates its effectiveness in predicting the femorotibial constraint behavior of TKA implants.

Introduction

TKA prostheses are semi-constrained artificial joints. A well-functioning TKA prosthesis should be designed with a good balance between stability and mobility, meaning the femorotibial constraint of the artificial joint cannot be excessive or too lax. To assess the constraint behavior of a TKA prosthesis, physical testing is usually required, and an industrial test standard has been developed for this purpose. Benefiting from technological advancement, computer simulation has become increasingly useful in many industries, including medical device research and development. FEA has been extensively used in stress analysis and structural evaluation of various orthopaedic implants. This study presented an FEA-based simulation to evaluate the femorotibial constraint behavior of TKA prosthesis, and demonstrated the effectiveness of the method by validating it through physical testing.


D. Bruni F. Iacono S. Bignozzi F. Colle M. Marcacci

Background

The optimal reference for rotational positioning of femoral component in total knee replacement (TKR) is debated. Navigation has been suggested for intra-op acquisition of patient's specific kinematics and functional flexion axis (FFA).

Questions/Purposes

To prospectively investigate whether pre-operative FFA in patients with osteoarthritis (OA) and varus alignment changes after TKR and whether a correlation exists between post-op FFA and pre-op alignment.


M.A. Shandiz P. Boulos S.K. Saevarsson S. Yoo C. Anglin

Summary Statement

A large proportion of knee arthroplasty patients are dissatisfied with their replacement. Significant differences exist between preoperative, postoperative and normal kinematics. A better understanding of the inter-relationships between kinematics, shape and prosthesis placement could lead to improved quality of life.

Introduction

Knee kinematics are altered by total knee arthroplasty (TKA) both intentionally and unintentionally. Knowledge of how and why kinematics change may improve patient outcome and satisfaction through improved implant design, implant placement or rehabilitation. Comparing preoperative to postoperative kinematics and shape of the natural and replaced joint will allow an investigation of the inter-relationships between knee shape, prosthesis placement, knee kinematics and quality of life.


A. Porter B. Snyder P. Franklin D. Ayers

Summary Statement

A prospective randomised evaluation of primary TKA utilizing patient specific instruments demonstrated great accuracy of bone resection, improved sagittal alignment and the potential to improve functional outcomes and reduce operating room costs when compared to standard TKA instrumentation.

Introduction

Patient specific instruments (PSI), an alternative to standard total knee arthroplasty (TKA) technology, have been proposed to improve the accuracy of TKA implant placement and post-operative limb alignment. Previous studies have shown mixed results regarding the effectiveness of PSI. The purposes of this study were (1) to evaluate the accuracy of the pre-operative predicted PSI plan compared to intra-operative TKA resection measurements, (2) to compare patient-reported outcome measures of PSI and standard TKA patients, and (3) to compare the incremental cost savings with PSI.


M. Bostrom H.-W. Courtland M. Grosso J. Sutherland K. Stoner X. Yang M. van der Meulen

Summary Statement

The modulation of both quantity and quality of peri-implant bone with either PTH or loading may be viable options to improve implant fixation and patient outcomes.

A strong bone-implant interface is essential for successful joint replacement surgery. This study investigated the differences in bone surrounding and within a porous titanium implant after single or combined treatment with two anabolic bone therapies: intermittent parathyroid hormone (teriparatide) and mechanical loading. Porous titanium implants were inserted bilaterally on the distal lateral femurs of rabbits. The right implant was loaded daily (1 MPa, 50 cycles/day) while the left implant was not. Rabbits received daily PTH injections (20 ug/kg) or saline vehicle. Periprosthetic cancellous bone 0.5, 1.0, and 2.0 mm below the implant surface, bone at the 0.25 mm bone-implant interface and total bone within each implant were examined using tissue-level analyses (quantitative backscattered electron microscopy), cellular analyses (immunohistochemistry staining of osteoblasts with procollagen-1 and TRAP staining of osteoclasts), and shear testing (implant-bone interface).

Statistical significance was determined using GEE models (p<0.05). For tissue located 0.5 mm below the implant, significant increases in bone area per total area (BA/TA) were observed with PTH treatment (56%) and with loading (27%). Further, an 18% increase in mineralization density with PTH treatment and a 20% increase in mineralization density with loading was found. Loading effects were not present beyond the 0.5 mm periprosthetic region, but PTH significantly increased BA/TA 2.0 mm below and mineralization density 1.0 mm below the implant. Tissue-level changes were supported by increases in osteoblast activity 0.5 mm below the implant with PTH (79%) and loading (34%), as well as by minimal osteoclast changes. At the 0.25 mm implant-bone interface PTH and loading increased BA/TA (16% and 23%, respectively), but only loading increased mineralization density (7%). Further, total integrated bone area was increased 35% with PTH.

Both PTH and loading enhanced the mechanical integrity of the implant-bone; shear strength increased 34% and 60%, respectively. Although combined treatment was not synergistic, both PTH and loading individually enhanced the amount and mineralization density of bone at the implant interface and immediately below the interface, thereby increasing the mechanical strength of the metal-bone interface. This research suggests that modulation of both quantity and quality of peri-implant bone may be viable options to improve implant fixation and patient outcomes.


C. Brockett S. Carbone L. Jennings J. Fisher

Summary Statement

Wear of total knee replacement (TKR) is a clinical concern. This study demonstrated low-conformity moderately cross-linked-polyethylene fixed bearing TKRs showed lower volumetric wear than conventional-polyethylene curved fixed bearing TKRs highlighting potential improvement in TKR performance through design and material selection.

Introduction

Wear of total knee replacement (TKR) continues to be a significant factor in the clinical performance of the implants. Historically, failure due to delamination and fatigue directed implant design towards more conforming implants to reduce contact stress. However, the new generations of more oxidatively-stable polyethylene have improved the long-term mechanical properties of the material, and therefore allowed more flexibility in the bearing design. The purpose of this study was to investigate the effect of insert conformity and material on the wear performance of a fixed bearing total knee replacement through experimental simulation.


S. Goel G.K. Jha N.K. Agarwal

Summary

Arginine supplementation is helpful in treatment of osteoporosis.

Introduction

Nitric oxide (NO) is a short-lived free radical involved in several biological processes as a bioregulator and as a second messenger. It inhibits osteoclastic bone resorption in vitro and regulates bone remodeling. Zolendronic acid has been established as a treatment for post menopausal osteoporosis. Study was done to compare the efficacy of Nitic oxide donor (L-arginine) with that of Zolendronic acid for the treatment of osteoporosis.


G. Di Pompo D. Granchi F. Poli B. Lorenzi M. Mandrone N. Baldini

Summary Statement

In this study it has been considered an alternative therapeutic approach to bone resorption diseases by using plant decoctions to improve adherence from patients to the treatment. In this context, Hemidesmus indicus represents a possible therapeutic or adjuvant natural compound.

Introduction

The acceleration of bone remodelling, with an excessive osteoclastogenesis or activation of mature osteoclasts, causes the loss of bone mass which is implicated in bone resorption diseases. Conventional therapies are expensive and limited by systemic toxicity and low drug bioavailability. Alternative treatments that are not only effective but also administered employing formulations and dosages different from conventional ones, may improve adherence to therapy, having a positive influence on clinical outcomes. Experimental evidence have attributed antiproliferative and apoptosis inducing activity on different cell lines (including osteoclast precursors or mature osteoclasts) to four plants used in Ayurvedic medicine: Asparagus racemosus (AR), Emblica officinalis (EO), Hemidesmus indicus (HI) and Rubia cordifolia (RC) These properties could be helpful in the treatment of some bone resorption diseases. In order to clarify the possible therapeutic effects of these compounds, the anti-osteoclast activity of their decoctions were evaluated.


S.-Y. Kim J.M. Hong H.-J. Yoon B.-M. Kwon I.-K. Lee H.-J. Kim

Summary Statement

Obovatol inhibits receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis and prevents inflammatory bone loss in mice

Introduction

Adult skeletal mass and integrity are maintained by balancing osteoclast-mediated bone resorption and osteoblast-induced bone formation during bone remodeling. Abnormal increases in osteoclastic bone resorption can lead to excessive bone destruction as observed in osteoporosis, rheumatoid arthritis, and metastatic cancers Therefore, Modulation of osteoclast formation and function is a promising strategy for the treatment of bone-destructive diseases. To search for compounds that inhibit osteoclast formation, we tested the effect of obovatol, a natural product isolated from the medicinal plant Magnolia obovata, on osteoclastogenesis and inflammatory bone loss.


B. Guo X. Wang A. Hong A. Lu B. Zhang G. Zhang

Summary Statement

The stable inhibition of miR-214 in the aged osteoporotic rats induced by OVX could be achieved by periodic administration of AntagomiR-214 at a dosage of 4 mg/kg and at an interval of 7 days, which will provide a potential bone anabolic strategy for treatment of osteoprosis.

Introduction

MiR-214 has a crucial role in suppressing bone formation and miR-214 inhibition in osteogenic cells may be a potential anabolic strategy for ameliorating osteoporosis (Wang X, et al. 2013). An aged ovariectomised rat has been regarded as a golden model to test bone anabolic agents for reversing established osteoporosis in aged postmenopausal women (Li X, et al. 2009). However, there is still lack of evidence to demonstrate bone anabolic potential of therapeutic inhibition of miR-214 within osteogenic cells in the golden model. So, it should be necessary to establish RNAi-based administration protocol toward stable inhibition of miR-214 at a low level in the golden model. A targeted delivery system specifically facilitating Antagomir-214 approaching osteogenic cells, i.e. (Asp-Ser-Ser)6-liposome (Zhang G, et al 2012), was employed in this study.


O. Emohare A. Cagan A. Dittmer J. Switzer D. Polly

Summary Statement

It is now possible to diagnose osteoporosis using incidental abdominal CT scans; applying this approach to fractures of the cervical spine demonstrates levels of osteoporosis in patients over 65.

Introduction

Recently published data now makes it possible to screen for osteoporosis in patients who, in the course of their hospital stay, have had Computed Tomography (CT) scans of their abdomen for reasons other than direct imaging. This is as a result of CT derived bone mineral density (BMD) in the first lumbar vertebra (L1) being correlated BMD derived from Dual-energy X-ray absorptiometry (DEXA) scans. The advantage of this is the reduction in both cost and radiation exposure. Although age has a detrimental effect on BMD, relatively few patients have formal DEXA studies. The aims of this study were to evaluate the utility of this new technique in a cohort of patients with acute fractures of the cervical spine and to compare relative values for BMD in patients aged over 65 with those aged under 65, and thus define the role of osteoporosis in these injuries.


O. Emohare A. Cagan A. Dittmer R. Morgan J. Switzer D. Polly

Summary Statement

Using abdominal CT scans to evaluate bone mineral density following acute fractures of the thoracic and lumbar spine demonstrates significant levels of osteoporosis in older patients; this approach may help save on time and resources, and reduce unnecessary radiation exposure.

Introduction

While a reduction in bone mineral density (BMD) is associated with aging, relatively few patients have formal dual-energy X-ray absorptiometry (DXA) to quantify the magnitude of bone loss, as they age. This loss of bone may predispose to fractures. Recent data, which correlates mean Hounsfield units (HU) in an area of the L1 vertebra with BMD, now makes it possible to screen for osteoporosis using incidental abdominal Computed Tomography (CT) scans to measure bone density. This innovation has the potential to reduce both cost and radiation exposure, and also make it easier to identify patients who may be at risk. The aims of this study were to evaluate the utility of this approach in patients with acute thoracic and lumbar spine fractures and to evaluate the impact of aging on BMD, using CT screening.


O. Emohare A. Dittmer A. Cagan D. Polly E. Gertner

Summary Statement

It is now possible to diagnose osteoporosis using incidental CT scans; this approach has been used to objectively demonstrate the role of osteoporosis in fracture in ankylosing spondylitis patients.

Background

In advanced disease, Ankylosing Spondylitis (AS) is frequently associated with a reduction in bone mineral density (BMD), this contributes to pain and predisposes to fractures. Quantifying this reduction in BMD is complicated by the simultaneous processes occurring, in which there is both an overgrowth of bone (syndesmophytes) and a concurrent loss of trabecular bone. Traditional methods such as dual-energy X-ray absorptiometry (DXA) struggle to generate accurate estimates for BMD in these patients. It has recently become possible to diagnose osteoporosis, with a high sensitivity and specificity, using incidental CT scans of the L1 vertebra. The purpose of this study was to evaluate the use of opportunistic CT screening in the diagnosis of osteoporosis in patients with AS who had sustained vertebral fractures.


A. Binch K. Phillips N. Chiverton A. Cole L. Breakwell A. Michael A. Cross C. Le Maitre

Summary

Cytokines produced within the degenerate disc induce expression of neurotrophic factors and pain related peptides which could be important in nerve ingrowth and pain sensitisation leading to low back pain.

The intervertebral disc (IVD) is considered the largest aneural and avascular structure within the human body, yet during degeneration vascularisation of the IVD is seen to be accompanied by nociceptive nerves. Low back pain is a highly debilitating condition affecting around 80% of the population, 40% of which are attributed to IVD degeneration. Discogenic pain was largely thought to be a result of irritation and compression of the nerve root, yet recent data suggests that pain may be attributed to the sensitisation of sensory nerves by the synthesis of pain related peptides, calcitonin gene related peptide (CGRP) and substance P. It is known that cytokines and chemokines produced by nucleus pulposus cells elicit various effects including the production of matrix degrading enzymes, and decreased matrix molecules. Here, we investigate the hypothesis that cytokines regulate both neurotrophic factor and pain related peptide synthesis within nucleus pulposus and nerve cells which may elicit algesic effects.

Real-Time PCR was performed to investigate gene expression of the neurotrophic factors NGF, BDNF, NT3 and their receptors Trk A, B and C along with Substance P and CGRP on directly extracted RNA from human NP cells and NP cells cultured in alginate for 2 weeks prior to treatment for 48hours with IL-1, IL-6 or TNFα at 0–100ng/mL. Similarly SH-SY5Y neuroblastoma cells were differentiated in retinoic acid for 7 days prior to stimulation with IL-1, IL-6 or TNFα at 0ng/mL and 10ng/mL for 48hours. Immunohistochemistry was used to localise neurotrophic factor receptors Trk A, B and C in both degenerate discs and neuronal cells.

NGF expression was present in normal and degenerate disc samples, however only degenerate discs expressed the high affinity receptor TrkA. Similarly Trk B was present in 22% of normal samples increasing to 100% expression within degenerate disc samples. All cytokines increased expression of NGF in NP cells (P≤0.05). TNFα also increased BDNF significantly, whereas no significant affects were seen in NT3 expression in NP cells. Trk B expression was significantly increased by IL-1 and TNFα treatment of NP cells. Conversely Trk C was down regulated by IL-6. Substance P was significantly increased by IL-1 and TNFα treatments whilst IL-6 and TNFα increased CGRP expression in NP cells. In SH-SY5Y cells, IL-1 significantly increased BDNF whilst IL-6 and TNFα failed to induce significant differences in neurotrophic factors. All cytokines increased Trk expression in the nerve cell line; however this failed to reach significance. Immunohistochemistry confirmed the presence of Trk receptors within the neuronal cell line.

Here we have demonstrated that a number of cytokines known to be up regulated during disc degeneration and disc prolapse, induce expression of various neurotrophic factors, their receptors and pain related peptides within human NP cells, as well as SH-SY5Y cells. This data suggests that the presence and production of cytokines within the degenerate disc may be responsible for nerve ingrowth and sensitisation of nerves which may result in discogenic pain.


K. Larsson C. Nordborg C. Örndal H. Brisby B. Rydevik

Introduction

In degenerative disorders of the spine such as disc herniation, intervertebral discs can affect neural tissue, which may result in pain as demonstrated in both basic science and clinical investigations. Previous in vitro and in vivo studies have shown that notochordal cells and chondrocyte-like cells in nucleus pulposus affect nervous tissue differently. The aim of the present study was to evaluate the morphology of spinal neural tissue in an in vivo rat model following application of cells derived from nucleus pulposus.

Material and method

A disc herniation model in rats (n=58) was used. The L4 nerve root was exposed to a) nucleus pulposus (3mg), b) notochordal cells (25,000 cells) or c) chondrocyte-like cells (25,000 cells). Four control groups were included: 1) application of nucleus pulposus (3 mg) and mechanical displacement of the spinal nerve complex, 2) sham operated animals, 3) application of cell diluent (50 μl) and 4) naïve animals. Seven days after surgery the L4 nerve roots with their dorsal root ganglion were harvested and prepared for blinded neuropathological examinations using light microscopy.


L.A. Nasto D. Wang A. Rasile Robinson K. Ngo E. Pola G. Sowa P. Robbins J. Kang L. Niedernhofer N. Vo

Summary Statement

DNA damage induced by systemic drugs or local γ-irradiation drives disc degeneration and DNA repair ability is extremely important to help prevent bad effects of genotoxins (DNA damage inducing agents) on disc.

Introduction

DNA damage (genotoxic stress) and deficiency of intracellular DNA repair mechanisms strongly contribute to biological aging. Moreover, aging is a primary risk factor for loss of disc matrix proteoglycan (PG) and intervertebral disc degeneration (IDD). Indeed, our previous evidences in DNA repair deficient Ercc1−/Δ mouse model strongly suggest that systemic aging and IDD correlate with nuclear DNA damage. Thus the aim of the current study was to test whether systemic or local (spine) genotoxic stress can induce disc degeneration and how DNA repair ability could help prevent negative effects of DNA damage on IDD. To test this hypothesis a total of twelve Ercc1−/Δ mice (DNA repair deficient) and twelve wild-type mice (DNA repair competent) were challenged with two separate genotoxins to induce DNA damage, i.e. chemotherapeutic crosslinking agent mechlorethamine (MEC) and whole-body gamma irradiation. Local effects of gamma irradiation were also tested in six wild-type mice.


A. Malandrino D. Lacroix J. Noailly

Summary Statement

An organ culture experiment was simulated to explore the mechanisms that can link cell death to mechanical overload in the intervertebral disc. Coupling cell nutrition and tissue deformations led to altered metabolic transport that largely explained cell viability measurements.

Introduction

Part of intervertebral disc (IVD) maintenance relies on limited nutrient availability to the cells and on mechanical loads, but effective implication of these two factors is difficult to quantify. Theoretical models have helped to understand the link between solute transport and cell nutrition in deforming IVD, but omitted the direct link between tissue mechanics and cell metabolism. Hence, we explored numerically the relation between disc mechanics and cell death in relation to an organ culture experiment.


R. Hart M. Komzák M. Puskeiler P. Jajtner

Background

Posterolateral fusion (PLF) is a commonly accepted surgical procedure and overall the most common technique performed to obtain fusion in the lumbar spine. Harvesting autologous bone from the iliac crest is associated with increased operation time, blood loss, and chronic donor site pain. Allograft material has an insufficient osteoinductive potential. Bone marrow concentrate (BMC) could be an option how to promote allograft PLF healing. The purpose of the presented study was to investigate the validity of BMC addition to allografts in instrumented lumbar PLF surgery.

Methods

The study was prospective, randomised, controlled and blinded. Eighty patients with degenerative disease of the lumbar spine underwent instrumented (S4, Aesculap, Tuttlingen, Germany) lumbar or lumbosacral PLF. In forty cases, the PLF was done with spongious allograft chips alone (Group I). In another forty cases, spongious allograft chips were mixed with BMC (Group II), where the mesenchymal stem cell (MSCs) concentration was 1.74 × 104/L at average (range, 1.06–1.98 × 104/L). Patients were scheduled for anteroposterior and lateral radiographs at 12 and 24 months after the surgery and for CT scanning at 24 months after the surgery. Fusion status and the degree of mineralization of the fusion mass were evaluated separately by two radiologists blinded to patient group affiliation.


H. Lu J. Hu J. Zhou Z. Zeng Y. Cao C. Chen

Summary Statement

We successfully delineated the 3D micro morphology of chondrocytes in patella-patellar tendon using IL-XPCT for the first time. Compared with conventional histology, IL-XPCT can not only provide a higher resolution imgaing but also keep the 3D integrity of the specimen.

Introduction

The morphology of the bone-tendon junction was complex and quite different from other organs, which result the injured bone-tendon junction repair process too slowly. To study the micro morphology of the bone-tendon junction in 3D may have a great significant value to revealing the repair mechanisms of this pathological process and accelerating injured bone-tendon junction repair. However, it was hindered by the convention methods such as histologic section. In our study, a novel imaging tool, synchrotron radiation based in-line x-ray phase contrast imaging (IL-XPCT) was used to research the 3D micro morphology of the bone-tendon junction.


S.A. Müller A. Todorov M. Majewski

Summary

We found an increased natural expression of the growth factors bFGF, BMP-12, VEGF, and TGF-b1 during tendon healing of rat Achilles tendons. External application of these growth factors improved the tendons failure load in the early healing phase.

Introduction

Tendon ruptures recover slowly and the healing of injuries can be devastating. Growth factors are known to influence tendon healing. However, only little is understood about growth factors in a healing tendon. Aim of this study was to investigate the influence of growth factors on tendon healing of rats following their natural expression.


E. Garvican S. Cree L. Bull R. Smith J. Dudhia

Summary Statement

Transportation media and injection protocol have implications for the viability of MSCs used for intra-lesional treatment of tendon injuries. Every effort should be made to implant cells within 24h of laboratory re-suspension, using a needle bore larger than 21G.

Introduction

Intra-lesional implantation of autologous mesenchymal stem cells (MSCs) has resulted in significant improvements in tendon healing in experimental animal models. Intra-tendinous injection of MSCs into naturally-occurring equine tendon injuries has been shown to be both safe and efficacious1 and these protocols can assist in the translation to the human. Efficient transfer of cells from the laboratory into the tissue requires well validated techniques for transportation and implantation. The aim of this study was to determine the influence of transport media and injection procedure on cellular damage.


M. Viganò D. Stanco S. Setti E. Galliera V. Sansone L. de Girolamo

Summary

In an in vitro tendon cell model, the tendon-specific gene expression up-regulation induced by PEMF negatively correlates with field intensity; moreover repeated lower-intensity PEMF treatments (1.5 mT) provokes a higher release of anti-inflammatory cytokines respect to the single treatment.

Introduction

Tendon disorders represent a diagnostic and therapeutic challenge for physicians. Traditional treatments are characterised by a long recovery time and a high occurrence of injury relapses. Despite the growing clinical interest in pulsed electromagnetic fields (PEMFs) few studies on their effect on tendons and ligaments have been conducted. Tendon resident cells (TCs) are a mixed population, made up mostly by tenocytes and tendon stem/progenitor cells, which are responsible of the tissue homeostasis. Since studies on the effect of PEMFs on this cell population are conflicting, we evaluated the possible relation between PEMFs dosage and TCs’ response. In particular, we compared the in vitro effect of low and high PEMFs on TCs (PEMF-1.5 mT; PEMF-3 mT); moreover we assessed the results of repeated treatments (R-PEMF-1.5mT).


M. Morrey E. Lostis S. Franklin O. Hakimi P.-A. Mouthy N. Zargar Baboldashti A. Carr

Summary Statement

A novel biomimetic polydioxanone tendon patch with woven and electrospun components is biocompatible, recapitulates native tendon architecture and creates a tissue-healing microenvironment directed by a subpopulation of regenerative macrophages. The woven component provides tensile strength while the tendon heals.

Introduction

There is great interest in the use of biomimetic devices to augment tendon repairs. Ideally, implants improve healing without causing adverse local or systemic reactions. Biocompatibility remains a critical issue prior to implantation into humans, as some implants elicit a foreign body response (FBR) involving inflammation, poor wound healing and even fistulae formation. Additionally, the effect on articular cartilage locally or systemically with placement of a juxta-articular implant has not been examined. The purpose of this study is to test the in vivo biocompatibility of a novel hybrid woven and electrospun polydioxanone patch in a rat tendon transection model.


H. Takeuchi H. Enomoto H. Matsunari K. Umeyama H. Nagashima T. Yoshikawa Y. Okada Y. Toyama Y. Suda

Summary

A novel in vivo animal model to establish new surgical interventions for patients with ACL insufficiency.

Introduction

After ACL reconstruction, recruited cells from surrounding tissues play crucial roles in ligamentization to obtain adequate structural properties. To allow athletes to return sports activity sooner, these remodeling processes should be elucidated and be accelerated. However, in conventional animal models, it has been difficult to differentiate donor and recipient cells. Here we introduce the transgenic Kusabira-Orange pigs, in which cells produce fluorescence systemically, as in vivo model to trace cell recruitment after ACL reconstruction.


D. Ayers L. Harrold W. Li J. Allison P. Noble P. Franklin

Summary Statement

This data may help explain the variability in physical function after primary TKR as compared to primary THR.

Introduction

Total knee replacement (TKR) and total hip replacement (THR) reliably relieve pain, restore function, and ensure mobility in patients with advanced joint arthritis; however these results are not uniform across all patient populations. We compared baseline demographic and symptom profiles in patients from a US national cohort undergoing primary TKR and THR.


L. Theelen N. Wentink Y. Dhooge R. Senden W. Hemert van B. Grimm

Summary

Movement analysis (IMA) and activity monitoring (AM) using a body-fixed inertia-sensor can discriminate patients with ankle injuries from controls and between patients of different pathology or post-injury time. Weak correlations with PROMs show its added value in objectifying outcome assessment.

Introduction

Ankle injuries often result in residual complaints calling for objective methods to score outcome alongside subjective patient-reported outcome measures (PROMs). Inertial motion analysis (IMA) and activity monitoring (AM) using a body-fixed sensor have shown clinical validity in patients suffering knee, hip and spine complaints. This study investigates the feasibility of IMA and AM 1) to differentiate patients suffering ankle injuries from healthy controls, 2) to compare different ankle injuries, 3) to monitor ankle patients during recovery.


W. Rea I. McCarthy P. Smitham

Summary

Cognitive testing scores do not correlate with physical braking performance. Psychological questioning shows patients are more dependent on driving than a control group.

Introduction

Returning to driving after surgery is a multifaceted issue. There are the medical aspects to consider- whether the patient is medically fit to drive. The term ‘medically fit to drive’ can encompass a range of issues which fall to doctors to solve, including the psychological and mental wellbeing. Groups whose governance involves patients or driving do not issue sound advice for patients or doctors to follow. Investigation of aspects affecting a driver's ability to control their vehicle in a safe manner could go towards providing an evidence base for guidance to be issued in the future.


D. Hamilton J. Lane P. Gaston J. Patton D. MacDonald H. Simpson C. Howie

Summary Statement

Service industry metrics (the net promoter score) are being introduced as a measure of UK healthcare satisfaction. Lower limb arthroplasty, as a ‘service’, scores comparably with the most successful commercial organisations.

Background

Satisfaction with care is important to both the patient and the payer. The Net Promoter Score, widely used in the service industry, has been recently introduced to the UK National Health Service as an overarching metric of patient satisfaction and to monitor performance. This questionnaire asks ‘customers’ if they would recommend a service or products to others. Scores range from −100 (everyone is a detractor) to +100 (everyone is a promoter). In industry, a positive score is well regarded, with those over 50 regarded as excellent. Our aims were to assess net promoter scores for joint arthroplasty, to compare these scores with direct measures of patient satisfaction, and to evaluate which factors contributed to net promoter response.


D. Hamilton N. Clement J. Patton R. Burnett P. Gaston C. Howie H. Simpson

Summary Statement

Using current analysis/methodology, new implant technology is unlikely to demonstrate a large enough change in patient function to impact on the cost-effectiveness of the procedure.

Purpose

Cost effectiveness is an increasingly important metric in today's healthcare environment, and decisions surrounding which arthroplasty prosthesis to implant are not exempt from such health economic concerns. Quality adjusted life years (QALYs) are the typical assessment tool for this type of evaluation. Using this methodology, joint arthroplasty has been shown to be cost effective, however studies directly comparing the QALY achieved by differing prostheses are lacking.


T. Ahmad

Summary Statement

With increasing emphasis on evidence-based medicine in healthcare, there is global increase in proportion of Level-1 and -2 articles in PUBMED. This study shows the trend of orthopaedic publications from different countries in comparison to other specialties.

Introduction

New medical knowledge is expected to improve health through change in existing practices. Articles need to convince readers of the validity of conclusions in order to bring about a change in practice. The last few decades have witnessed an increasing interest in critical appraisal of research aimed at assessing the ‘quality’ of evidence, a trend towards ‘Evidence Based Medicine’. Whether orthopaedic publications are also becoming more evidence-based has hitherto not been reported. This study aimed to compare the trend of publications originating from orthopaedic services versus other specialties, across different countries, with respect to major categories of levels of evidence.


E. Curry X. Li K. Buesser J. Nguyen E. Matzkin

Summary Statement

The purpose is to evaluate the effects of internet usage on new patient referral patterns to identify optimal patient recruitment and communication. Overall, social networking and internet may be an effective way for surgeons to recruit a wider patient population.

Introduction

Prior studies in other medical specialties have shown that social networking and internet usage has become an increasingly important means of patient communication and referral. However, this information is lacking in the orthopaedics literature. In this study, we evaluate the means by which new patients arrive at orthopaedic clinics in a major academic center. The purpose is to evaluate the effects of internet or social media usage on new patient referral patterns to identify avenues to optimise patient recruitment and communication.


C. Perez-Jorge R. Perez-Tanoira D. Lozano A. Conde M.-A. Arenas J.-M. Hernandez-Lopez J.-J. De-Damborenea E. Gomez-Barrena P. Esbrit J. Esteban

Summary Statement

Description of an original in vitro protocol for assessing combined bacteria and cell competitive adherence on the surface of biomaterials of medical interest

Objectives

Biomaterial-related infections are a major clinical problem. The pathogenesis of this syndrome has been described as a competitive adherence between bacteria and human cells in the so-called “race for the surface” theory. The aim of this study is to develop an in vitro protocol method that can be used to investigate this competence and its implications in the development of materials aimed to be used in orthopedic surgery.


J. Blackburn M. Skinderso K. Krogfelt A. Blom A. Lovering J. Mansell

Summary Statement

Developing titanium (Ti) surfaces that are biocompatible yet serve as deterrents for bacterial attachment and growth are particularly appealing in tackling the ongoing problem of sepsis-induced implant failures. Realising this could include coating Ti with the bioactive lipid, lysophosphatidic acid.

Introduction

Surgical revision for failed total joint replacements costs a staggering £300m/yr and approximately 20% of this burden is attributed to implant failure through bacterial infection. Producing biomaterials that deter microbial attachment as well as securing robust osseointegration continues to be a significant research challenge in contemporary bone biomaterials design. Steps to realising novel improvements are further compounded by the concerns raised over resistance of bacteria to many antimicrobial agents. Clearly this is a major constraint necessitating an entirely novel approach to minimising implant infection risk. We therefore turned our attention to certain lysophosphatidic acids (LPAs) for Ti functionalisation. We have found LPA to enhance calcitriol-induced human osteoblast (hOB) maturation. Of further significance is the discovery that LPA can directly inhibit the growth of certain bacteria and even co-operate with some antibiotics to bring about their demise. Herein we describe the fabrication of a hOB-compatible Ti surface with palmitoyl-LPA (P-LPA) which we also find hinders bacterial attachment.


H. Gbejuade A. Lovering A. Hidalgo-Arroyo J. Leeming J. Webb

Summary Statement

Conventional culture techniques have poor sensitivity for detecting bacteria growing in biofilms, which can result in under-diagnosis of infections. Sonication of biofilm colonised orthopaedic biomaterials can render bacteria in biofilm more culturable, thereby improving diagnosis of orthopaedic implant infections.

Introduction

Prosthetic joint infection (PJI) is a potentially devastating complication in arthroplasty. Biofilm formation is central to PJI offering protection to the contained bacteria against host defence system and antimicrobials. Orthopaedic biomaterials generally have a proclivity to biofilm colonisation. Conventional culture technique has a low sensitivity for detecting bacteria in biofilm. Sonication can disrupt bacteria biofilms aggregations and dislodge them from colonised surfaces, rendering them culturable and consequently improve the diagnosis of otherwise culture-negative PJI. We investigated the effect of ultrasonication on biofilms adherent to poylmethylmethacrylate PMMA cement.


D. Segal R. Estrada M. Pasion R. Ramos Y. Stark R. Gustilo N. Emanuel

Purpose

Gustilo type III open fractures are associated with high infection rates in spite of instituting a standard of care (SOC) consisting of intravenous antibiotics, irrigation and debridement (I&D), and delayed wound closure. Locally-delivered antibiotic has been proven to assist in reducing infection in open fractures. The aims of this study are to determine the effectiveness and safety of a new implantable and biodegradable antibacterial product1 in preventing bacterial infections and initiating bone growth in open fractures.

Methods

The osteoconductive antibacterial BonyPidTM used is a synthetic bone void filler (comprised of ≤1 mm β-tricalcium phosphate granules) coated by a thin layer (≤20 µm) of PolyPid nanotechnology formulation. Upon implantation, the coating releases doxycycline at a constant rate for a predetermined period of 30 days. One BonyPidTM vial of 10 grams contains 65 mg of formulated doxycycline. After approval, sixteen subjects with Gustilo type III open tibia fractures, were implanted with the BonyPidTM immediately on the first surgical intervention (I&D), followed by external fixation. Patients had periodic laboratory, bacteriology and radiology follow-up.


D. Molina-Manso G. Del-Prado M. Lucas-Diaz E. Gómez-Barrena J. Cordero-Ampuero J. Esteban

Summary Statement

Combination of antibiotics with N-acetylcisteine and sub-MIC concentration of erythromycin was evaluated in two collection and 16 clinical strains of staphylococci isolated from PJI. The results were strain-dependent, so it evidences the necessity of perform individual studies of biofilm susceptibility.

Objectives

Staphylococci are the most common cause of prosthetic joint infections (PJI) (1), making the treatment of this disease difficult due to the increased resistance to antibiotics of biofilms. Combination between antibiotics and other compounds could be a good alternative. The aim of this study was to evaluate the effect of the combination of two compounds with nine antibiotics in biofilms formed by staphylococcal strains isolated from PJI.


S.P. Morapudi R. Zhou K. Barnes

Summary

There is little knowledge in surgeons about the guidelines for prophylactic antibiotics in patients with prosthetic joints when undergoing a dental procedure. This study confirms this and there is need for robust and universal guidelines given the disastrous nature of prosthetic infection.

Introduction

Infection as an indication for revision has increased to 12 % of the total revisions (NJR 9th report). However, it is next to impossible to find out the cause for a delayed prosthetic infection. With increasing number of arthroplasty procedures, is there a need for prophylactic antibiotics in patients with prostheses?


F. Boriani R. Urso M. Fell A. Ul Haq U. Khan

Summary

open tibia fractures are best treated in an orthopaedic-plastic surgical multidisciplinary setting.

Introduction

Open fractures of the leg represent a severe trauma. It is often stated that combining the skills of Plastic and Orthopaedic surgeons can optimise the results of limb salvage in complex limb injury. The multidisciplinary approach, shared between plastic and orthopaedic surgeons, is likely to provide the optimal treatment of these injuries, although this mutidisciplinary simultaneous treatment is not routinely performed. Given the relatively low incidence of these traumas, a multicentric recruitment of these patients can contribute in providing an adequately numerous cohort of patients to be evaluated through the long process of soft tissue and bone healing following an open tibia fracture. We compared three centres with different protocols for management of these challenging cases.


Y. Ding Z. Guan J. Xu R. Ma

Summary

Osteoporosis reduces particle-induced osteolysis in rat model.

Introduction

Wear particle induced osteolysis is considered to be a vital factor that reduces the life span of joint prosthesis. Osteoporosis is not rare in patients with indication for arthroplasty. However, the influence of osteoporosis on wear particles induced osteolysis is not clear. This study is aimed to explore on this issue by using animal model.


S. Grosse P.J. Høl P.K. Lilleng H.K. Haugland G. Hallan

Summary

Particulate wear debris with different chemical composition induced similar periprosthetic tissue reactions in patients with loosened uncemented and cemented titanium hip implants, which suggests that osteolysis can develop independent of particle composition.

Introduction

Periprosthetic osteolysis is a serious long-term complication in total hip replacements (THR). Wear debris-induced inflammation is thought to be the main cause for periprosthetic bone loss and implant loosening. The aim of the present study was to compare the tissue reactions and wear debris characteristics in periprosthetic tissues from patients with failed uncemented (UC) and cemented (C) titanium alloy hip prostheses. We hypothesised that implant wear products around two different hip designs induced periprosthetic inflammation leading to osteolysis.


S. Goodman Z. Yao P.-G. Ren E. Gibon A. Rao J. Pajarinen J. Antonios T.-h. Lin R.L. Smith K. Egashira M. Keeney F. Yang Y. Konttinen

Summary

Wear particles from joint replacements may result in loosening and periprosthetic osteolysis. Interference with systemic macrophage trafficking to the implant, modulation of macrophage phenotype from M1 to M2, and inhibition of NFκB may mitigate these adverse effects.

Introduction

Joint replacement of the lower extremity is highly successful in alleviating pain, and improving ambulation and function. However, prosthetic byproducts of different materials, in sufficient amounts, may lead to loosening and periprosthetic osteolysis. Debris from polymers (such as polyethylene and PMMA), metals and ceramics are capable of inciting an adverse tissue reaction, which is orchestrated by cells of the monocyte/macrophage lineage. Three experimental approaches have been taken by our group to potentially mitigate the adverse biological sequela of particle disease. These include: 1) interfering with ongoing migration of monocyte/macrophages to the implant site by inhibiting the chemokine system 2) altering the functional activities of local macrophages by converting pro-inflammatory M1 macrophages to an anti-inflammatory pro-tissue healing M2 phenotype and 3) modulating the production and release of pro-inflammatory cytokines, chemokines and other potentially harmful factors by inhibiting the key transcription factor NFκB.


R.W. Li H.R. Patel D. Perriman J. Wang P.N. Smith

Summary Statement

Using the latest Next Generation Sequencing technologies, we have investigated miRNA expression profiles in human trabecular bone from total hip replacement (THR) revision surgery where wear particle associated osteolysis was evident.

Introduction

A major problem in orthopaedic surgery is aseptic loosening of prosthetic implants caused by wear particle associated osteolysis. Wear debris is known to impact on a variety of cellular responses and genes in multiple pathways associated with the development of the periprosthetic osteolysis. MicroRNAs (miRNAs) act as negative regulators of gene expression and the importance of miRNAs in joint pathologies has only recently been addressed. However, miRNA profiles in osteolytic bone are largely unknown. Using the latest Next Generation Sequencing technologies, we have investigated miRNA expression profiles in human trabecular bone sourced from bone discarded during total hip replacement (THR) revision surgery where wear particle associated osteolysis was evident.


Y. Ding C. Qin D. Huang H. Shen

Summary

RNAi targeting TNF-alpha inhibits particle-induced inflammation and osteolysis.

Introduction

Over 1000,000 joint prostheses are implanted every year in the world. Aseptic joint loosening is a key factor that reduces the longevity of joint prosthesis. Prosthetic wear particles are thought to play a central role in the initiation and development of periprosthetic osteolysis, leading to aseptic loosening of prostheses. This study aims to investigate the effect of RNA interference (RNAi) targeting tumor necrosis factor-alpha (TNF-α) gene on particle-induced inflammation and osteolysis in macrophages in vitro and in vivo.


I. Vanhegan M. Coathup I. McCarthy F. Haddad G. Blunn

Summary Statement

Proximal femoral bony deficits present a surgical and biomechanical challenge to implant longevity in revision hip arthroplasty. This work finds comparable primary stability when a distally fixing tapered fluted stem was compared with a conical design in cadaveric tests.

Introduction

Proximal bony deficits complicate revision hip surgery and compromise implant survival. Longer distally fixing stems which bypass such defects are therefore required to achieve stability compatible with bony ingrowth and implant longevity.


V. Moretti J. Thormeyer S. Chmell

Summary Statement

The circle theorem is a simple and effective measurement tool for estimating acetabular version after total hip arthroplasty

Introduction

Position of the acetabular cup is a major factor in the range of motion and risk of dislocation after total hip arthroplasty. However, there is no well established technique for accurately and easily estimating acetabular cup version intraoperatively or postoperatively. The objective of this study was to evaluate a recently proposed method for measuring acetabular cup version on a single plain radiograph of the hip, which is based on one of the circle theorems in basic geometry.


G. Trisolino A. Strazzari C. Stagni G. Tedesco U. Albisinni E. Martucci D. Dallari

Summary Statement

Pincer deformities are involved in the genesis of femoro-acetabular impingement (FAI). Radiographic patterns suggestive of pincer deformities are common among general population. Prevalence of the pincer deformities among general population may be overestimated if only plain radiographs are considered.

Background

Pincer deformities (coxa profunda, protrusio acetabuli, global retroversion, isolated cranial over-coverage) have been advocated as a cause of femoro-acetabular impingement (FAI) and early hip osteoarthritis (OA). Different radiographic patterns may advocate the presence of a pincer deformity. The prevalence of these radiographic patterns among general adult population, as their role in early hip OA, is poorly defined.


C. Lowry G. Vincent A. Traynor S. Collins

Summary Statement

Corin has developed bone conserving prosthesis (MiniHip™) to better replicate the physiological load distribution in the femur. This study assessed whether the MiniHip™ prosthesis can better match the pre-osteoarthritic head centre for patient demographics when compared to contemporary long stem devices.

Introduction

Leg length and offset discrepancy resulting from Total Hip Replacement (THR) is a major cause of concern for the orthopaedic community. The inability to substitute the proximal portion of the native femur with a device that suitably mimics the pre-operative offset and head height can lead to loss of abductor power, instability, lower back pain and the need for orthodoses. Contemporary devices are manufactured based on predicate studies to cater for the variations within the patient demographic. Stem variants, modular necks and heads are often provided to meet this requirement. The number of components and instruments that manufacturers are prepared to supply however is limited by cost and an unwillingness to introduce unnecessary complexity. This can restrict the ability to achieve the pre-osteoarthritic head centre for all patient morphologies. Corin has developed MiniHip™ to better replicate the physiological load distribution in the femur. This study assessed whether the MiniHip™ prosthesis can better match the pre-osteoarthritic head centre for patient demographics when compared to contemporary long stem devices.


R. Gwyn S. Mahmood I. Malik M. Maheson A. John C. Lyons S. Jones

Summary

162 patient cohort with serial Metal Artefact Reduction Sequence MRI scans. Patients with normal initial scans can be followed up at 1 year. Those with abnormal scans should be followed up at a shorter interval of 6 months.

Introduction

Cross-sectional imaging is a key investigation in the assessment and surveillance of patients with metal-on-metal (MoM) hip arthroplasty. We present our experience of Metal Artefact Reduction Sequence (MARS) MRI scanning in metal on metal hip arthroplasty. We aimed to investigate the natural history and radiological disease progression from Adverse Reactions to Metallic Debris.


Y. Lu K. Püschel M. Morlock G. Huber

Summary

At the clinical CT image resolution level, there is no influence of the image voxel size on the derived finite element human cancellous bone models

Introduction

Computed tomography (CT)-based finite element (FE) models have been proved to provide a better prediction of vertebral strength than dual-energy x-ray absorptiometry [1]. FE models based on µCTs are able to provide the golden standard results [2], but due to the sample size restriction of the µCT and the XtremeCT machines, the clinical CT-based FE models is still the most promising tool for the in vivo prediction of vertebrae's strength. It has been found [3] that FE predicted Young's modulus of human cancellous bone increases as the image voxel size increases at the µCT resolution level [3]. However, it is still not clear whether the image voxel size in the clinical range has an impact on the predicted mechanical behavior of cancellous bone. This study is designed to answer this question.


P. Vanden Berghe J. Demol F. Gelaude J. Vander Sloten

Summary

This work proposes a novel, automatic method to obtain an anatomical reconstruction for 3D segmented bones with large acetabular defects. The method works through the fitting of a Statistical Shape Model to the non-defect parts of the bone.

Introduction

Patient-specific implants can be used to treat patients with large acetabular bone defects (IIa-c, IIIb, Paprosky 1994). These implants require a full 3D preoperative planning that includes segmentation of volumetric images (CT or MRI), extraction of the 3D shape, reconstruction of the bone defect into its anatomic (non-defect) state, design of an implant with a perfect fit and optimal placement of the screws. The anatomic reconstruction of the bone defect will play a key role in diagnosing the amount of bone loss and in the design of the implant. Previous reconstruction methods rely on a healthy contralateral (Gelaude 2007); however this is not always available (e.g. partial scan or implant present). Statistical shape models (SSM) of healthy bones can help to increase the accuracy and usability of the reconstruction and will decrease the manual labor and user dependency. Skadlubowicz (2009) illustrated the use of an SSM to reconstruct pelvic bones with tumor defects; however tumors generally affect a smaller region of the bone so that the reconstruction will be easier than in large acetabular bone defects. Also, the tumor reconstruction method uses 80 manually indicated landmarks, while the proposed method only uses 14.


P. Garner R. Wilcox J. Aaron

Summary Statement

Prophylactic vertebroplasty treatment of ‘at-risk’ vertebrae may reduce fracture risk, however which areas weaken, thus providing surgical targets? Direct spatial 3D mapping of ReTm overcomes the constraints of 2D histology, and by application may provide insight into specific regional atrophy.

Introduction

Insidious bone loss with age makes the skeleton fracture-prone in the rapidly expanding elderly population. Diagnosis of osteoporosis is often made after irreversible damage has occurred. There are over 300,000 new fragility fractures annually in the UK, more than 120,000 of these being vertebral compression fractures (VCF). Some VCFs cause life-altering pain, requiring surgical intervention. Vertebroplasty is a minimally invasive procedure whereby bone cement is injected into the damaged vertebral body with the aim of stabilisation and pain alleviation. However, vertebroplasty can alter the biomechanics of the spine, apparently leaving adjacent vertebrae with an increased VCF risk. Prophylactic augmentation of intact, though ‘at-risk’, vertebrae may reduce the risk of adverse effects. The question therefore arises as to which areas of a non-fractured vertebral body, structurally weakened with age, and thus should be targeted. Frequent reports of an overlap in BMD (bone mineral density) between fracture and non-fracture subjects suggest the combination of bone quantity and its ‘quality’ (microarchitectural strength) may be a more reliable fracture predictor than BMD alone. Providing a reliable method of cancellous connectivity measurement (a highly significant bone strength factor) is challenging. Traditional histological methods for microarchitectural interconnection are limited as they usually indirectly extrapolate 3D structure from thin (8 µm) 2D undecalcified sections. To address this difficulty, Aaron et al (2000) developed a novel, thick (300 µm) slicing and superficial staining procedure, whereby unstained real (not stained planar artifactual) trabecular termini (ReTm) are identified directly within their 3D context.

The aim of this study was to automate a method of identifying trabecular regions of weakness in vertebral bodies from ageing spines. Patients and methods. 27 Embalmed cadaveric vertebral bodies (T10-L3) from 5 women (93.2±8.6 years) and 3 men (90±4.4 years) were scanned by µCT (micro-computerised tomography; µCT80, Scanco Medical, Switzerland, 74 µm voxel size), before plastic-embedding, slicing (300µm thick), and surface-staining with the von Kossa (2% silver nitrate) stain. The ReTm were mapped using light microscopy, recording their coordinates using the integrated stage, mapping them within nine defined sectors to demonstrate any apparent loci of structural disconnectivity that may cause weakness disproportionate to the bone loss. A transparent 3D envelope corresponding to the cortex, was constructed using code developed in-house (Matlab 7.3, Mathworks, USA), and was modulated and validated by overlay of the previous µCT scan and the coordinate data.


H. Wada H. Mishima K. Hyodo M. Yamazaki

Summary Statement

We used three-dimensional software to assess different anatomic variables in the femur. The canal of Femur twisted slightly below the lesser trochanter in cases with a larger angle of anteversion.

Introduction

Accurate positioning of the joint prosthesis is essential for successful total hip arthroplasty (THA). To aid in tailoring of the prosthesis, we used three-dimensional software to assess different anatomic variables in the femur.


C. Fitzpatrick L. Vigneron S. Kannan S. Shah X. (Cheryl) Liu S. De Boodt P. Rullkoetter

Summary Statement

Computational models are the primary tools for efficient design-phase exploration of knee replacement concepts before in vitro testing. To improve design-phase efficiency, a subject-specific computational platform was developed that allows designers to assess devices in realistic conditions by directly integrating subject-specific experimental data in these models.

Introduction

Early in the design-phase of new implant design, numerous in vitro tests would be desirable to assess the influence of design parameters or component alignment on the performance of the device. However, cadaveric testing of knee replacement devices is a costly and time-consuming procedure, requiring manufacture of parts, preparation of cadaveric specimens, and personnel to carry of the experiments. Validated computational models are ideally suited for pre-clinical, high-volume design evaluation. Initial development of these models requires substantial time and expertise; once developed, however, computational simulations may be applied for comparative evaluation of devices in an extremely efficient manner [Baldwin et al. 2012]. Still, computational models are complementary of experimental testing and for this reason, computational models tuned with subject-specific experimental data, e.g. soft tissue parameters, could bring even more efficiency in the design phase. The objective of the current study was to develop a platform of tools that easily allows for subject-specific knee simulations. The system integrates with commercially available medical imaging and finite element software to allow for direct, efficient comparison of designs and surgical alignment under a host of different boundary conditions.


M. Meijer A. Boerboom M. Stevens S. Bulstra I. Reininga

Summary

Computer assisted surgery (CAS) during total knee arthroplasty (TKA) is known to improve prosthetic alignment in coronal and sagittal plane. In this systematic review, no evidence is found that CAS also improves axial component orientation when used during TKA.

Introduction

Primary total knee arthroplasty (TKA) is a safe and cost-effective treatment for end-stage knee osteoarthritis. Correct prosthesis alignment is essential, since malpositioning of the prosthesis leads to worse functional outcome and increased wear, which compromises survival of the prosthesis. Computer assisted surgery (CAS) has been developed to enhance prosthesis alignment during TKA. CAS significantly improves postoperative coronal and sagittal alignment compared to conventional TKA. However, the influence of CAS on rotational alignment is a matter of debate. Therefore purpose of this review is to assess published evidence on the influence of CAS during TKA on postoperative rotational alignment.


O. Alizadehkhaiyat D. Hawkes A. Howard S. Frostick

Summary Statement

Bio-impedance analysis (BIA) provides a convenient method for the estimation of whole body and segmental measurement of skeletal muscle mass (SMM). BIA-measured SMM parameters may be effectively used for the normalisation of muscle strength and removing body-size dependence.

Introduction

Despite an increasing interest in using bio-impedance analysis (BIA) for the estimation of segmental skeletal muscle mass (SMM); existing data is sparse. On the other hand, there is a need for better understanding of the influence of SMM on gender-related differences in muscle strength. Using BIA technique, this study aimed to measure the SMM, determine its correlation with muscle strength, and examine its relation with gender-related differences in muscle strength.


K. Kishimoto E. Itoi

Summary Statement

Paraspinal muscle contain higher proportion of slow-twich fibers. The fixation of the rat tail induced transition of muscle fiber types in the paravertebral muscles characterised by the decrease in the proportion of the slow type myosin heavy chain.

Introduction

Lumbar degenerative kyphosis often accompanies back pain, easy fatigability, fatty degeneration and atrophy of back muscles. There are two types of skeletal muscle fibers according to oxidative activities: slow-twich (Type 1) and fast-twitch (Type 2) fibers. Type 2 fibers were subdivided into three types: Type 2A, 2B and 2D/X. Each fiber type primarily expresses a specific isoform of myosin heavy chain (MHC). It has been known that back muscles contain higher proportion of MHC type 1. However, the impact of kyphosis on the proportion of fiber types in the paravertebral muscles has not been fully understood. The aim of this study is to analyze the transition of muscle fiber types after kyophotic or straight fixation using a rat tail model.


C. Barrios V. Zena G. de Blas J. García-Casado L. Cabañes B. Catalán J. Burgos D. Noriega J. Saiz

Summary Statement

Patients with adolescent idiopathic scoliosis show clear signs of abnormal motor coordination between the long superficial paraspinal muscles and the deep rotators. These findings suggest an abnormal behavior of the deep rotator muscles at the concave side.

Introduction

An imbalance between the myoelectric activity of the muscles of the convexity and the concavity has been described in patients with adolescent idiopathic scoliosis (AIS). These findings are based on EMG patterns recorded with surface electrodes that do not distinguish between deep and superficial muscles. This work was aimed at analyzing the coupled behavior of the superficial and deep paraspinal muscles in subjects with AIS at both sides of the curve.


A. Gigante M. Cianforlini A. Busilacchi S. Manzotti M. Mattioli Belmonte

Summary Statement

This experimental study showed that platelet rich fibrin matrix can improve muscle regeneration and long-term vascularization without local adverse effects.

Introduction

Even though muscle injuries are very common, few scientific data on their effective treatment exist. Growth Factors (GFs) may have a role in accelerating muscle repair processes and a currently available strategy for their delivery into the lesion site is the use of autologous platelet-rich plasma (PRP). The present study is focused on the use of Platelet Rich Fibrin Matrix (PRFM), as a source of GFs.


R. James M. Hogan G. Balian A.B. Chhabra C.T. Laurencin

Summary Statement

A resorbable and biocompatible polymer-based scaffold was used for the proliferation and delivery of adipose derived stromal cells, as well as delivery of a cell growth/differentiation promoting factor for improved tendon defect regeneration.

Introduction

Surgeons perform thousands of direct tendon repairs annually. Repaired tendons fail to return to normal function following injury, and thus require continued efforts to improve patient outcomes. The ability to produce regenerate tendon tissue with properties equal to pre-injured tendon could lead to improved treatment outcomes. The aim of this study was to investigate in vivo tendon regeneration using a biodegradable polymer for the delivery of adipose derived stromal cells (ADSCs) and a polypeptide, growth/differentiation factor-5/(GDF-5), in a tendon gap model.


S. Alqahtani E. Harvey J. Henderson V. Chodavarapu Y. Wang C. Allan

Significance

Acute compartment syndrome (ACS) occurs after muscle injury and is characterised by increased pressure in the muscle compartment that can result in devastating complications if not diagnosed and treated appropriately. ACS is currently confirmed by repeated needle sticks to measure the compartment pressure using a hand-held compartment pressure monitor. This approach is often not reproducible and is not appropriate for continuous monitoring. To address the shortcomings of currently available technology we are developing an implantable micro-device that will measure compartment pressure directly and continuously over the 24 hours critical period following injury using a radio frequency identification (RFID) platform integrated with a MEMS capacitive pressure sensor.

Methods

The prototype implantable device measuring 3mmx3mm consists of a capacitive pressure sensor, a sensor readout circuitry, an antenna and a radio frequency reader. A prototype sensor was packaged in Silicone gel (MED-6640, Nusil Technology LLC) for ex vivo and in vivo testing in three compartment models. First, it was tested ex vivo in an airtight vessel using a blood pressure monitor to pump air and increase the pressure inside the vessel. Second, it was implanted in a muscle compartment of a fresh porcine hind limb and an infusion pump with normal saline was used to raise the tissue pressure. Third, it was implanted in the posterior thigh muscle of a rat where the pressure was increased by applying a tourniquet around the thigh. The readings were compared with those from a hand-held Stryker Intra-compartmental Pressure Monitor System used in the trauma room.


M.P. Abdel M.E. Morrey J.D. Barlowv D.E. Grill C.P. Kolbert K.-N. An S.P. Steinmann B.F. Morrey J. Sanchez-Sotelo

Summary

Based upon genetic analysis, decorin is an exciting pharmacologic agent of potential anti-fibrogenic effect on arthrofibrosis in our animal model.

Introduction

While the pathophysiology of arthrofibrosis is not fully understood, some anti-fibrotic molecules such as decorin could potentially be used for the prevention or treatment of joint stiffness. The goal of this study was to determine whether intra-articular administration of decorin influences the expression of genes involved in the fibrotic cascade ultimately leading to less contracture in an animal model.


A. Marmotti S. Mattia G.M. Peretti D. Bonasia M. Bruzzone F. Dettoni R. Rossi L. Mazzucchelli D. Gioia F. Castoldi

Summary Statement

Mesenchymal stem cells from minced umbilical cord fragments may represent a valuable cell population for cartilage and bone tissue engineering

Introduction

A promising approach for cartilage and bone repair is the use of umbilical cord mesenchymal stem cell (UC-MSC)-based tissue engineering. Through a simple and efficient protocol based on mincing the umbilical cord, a consistent number of multipotent UC-MSCs can be obtained. The aim of this in-vitro study is to investigate the pluripotency of UC-MSCs and, in particular, the chondrogenic and osteogenic potential of UC-MSCs grown in tridimensional scaffold, in order to identify a potential clinical relevance for patients who might benefit from MSCs-therapy.


S. Lopa A. Colombini D. Stanco L. de Girolamo V. Sansone M. Moretti

Summary

The donor-matched comparison between mesenchymal stem cells from knee infrapatellar and subcutaneous adipose tissue revealed their preferential commitment towards the chondrogenic and osteogenic lineage, respectively. These peculiarities could be relevant for the development of successful bone and cartilage cell-based applications.

Introduction

Mesenchymal stem cells (MSCs) have been proposed in bone and cartilage tissue engineering applications as an alternative to terminally differentiated cells. In the present study we characterised and performed a donor-matched comparison between MSCs resident within the infrapatellar fat pad (IFP-MSCs) and the knee subcutaneous adipose tissue (ASCs) of osteoarthritic patients. These two fat depots, indeed, can be considered appealing candidates for orthopaedic cell-based therapies since they are highly accessible during knee surgery.


L. Kuntz J. Tuebel C. Marthen F. Hilz R. von Eisenhart-Rothe R. Burgkart

Introduction

Despite the high regenerative capacity of bone, large bone defects often require treatment involving bone grafts. Conventional autografting and allografting treatments have disadvantages, such as donor site morbidity, immunogenicity and lack of donor material. Bone tissue engineering offers the potential to achieve major advances in the development of alternative bone grafts by exploiting the bone-forming capacity of osteoblastic cells. However, viable cell culture models are essential to investigate osteoblast behavior. Three-dimensional (3D) cell culture systems have become increasingly popular because biological relevance of 3D cultures may exceed that of cell monolayers (2D) grown in standard tissue culture. However, only few direct comparisons between 2D and 3D models have been published. Therefore, we performed a pilot study comparing 2D and 3D culture models of primary human osteoblasts with regard to expression of transcription factors RUNX2 and osterix as well as osteogenic differentiation.

Patients and Methods

Primary human osteoblasts were extracted from femoral neck spongy bone obtained during surgery procedures. Primary human osteoblasts of three donor patients were cultured in monolayers and in three different 3D culture models: 1) scaffold-free cultures, also referred to as histoids, which form autonomously after multilayer release of an osteoblast culture; 2) short-term (10-day) collagen scaffolds seeded with primary human osteoblasts (HOB); 3) long-term (29-day) collagen scaffolds seeded with HOB. Expression levels of transcription factors RUNX2 and osterix, both involved in osteoblast differentiation, were investigated using quantitative PCR and immunohistochemical staining. Furthermore, markers of osteogenic differentiation were evaluated, such as alkaline phosphatase activity, osteocalcin expression, and mineral deposition, as well as the expression of collagen type I and fibronectin extracellular matrix proteins.


J. Twomey A. Hsieh

Summary

This study helps to elucidate how ColVI and Dcn within the pericellular matrix (PCM) of differentiating hMSCs directly impacts dynamic cytoskeletal response to load, and demonstrates an important role for the PCM in mechanotransduction during chondrogenesis.

Introduction

Mechanosignaling events in differentiating human mesenchymal stem cells (hMSCs) are dependent on their temporally changing micromechanical environment and their dynamic cytoskeleton. During chondrogenic differentiation, hMSCs develop a matrix composed of type VI collagen (ColVI) and proteoglycans such as decorin (Dcn). We have previously demonstrated that this developing PCM is important in cellular mechanotransduction. The aim of this study was to determine the functional roles of ColVI and Dcn in modulating load-induced changes in the organization of vimentin intermediate filaments (VIF), actin microfilaments (AM), and vinculin.


J. Lai G. Kajiyama R.L. Smith W. Maloney F. Yang

Summary Statement

This work raises the potential of utilizing stem cells to catalyze cartilage regeneration by a minimal number of neonatal chondrocytes via controlling cell distribution in 3D matrices, and may solve the challenge of scarce donor availability associated with cell-based therapy.

Introduction

Cartilage loss is a leading cause of disability among adults and represents a huge socio-economical burden. Allogeneic neonatal articular chondrocytes (NChons) is a promising cell source for cartilage regeneration because these cells are highly proliferative, immune-privileged, and readily produce abundant cartilage matrix. However, scarce donor availability for NChons greatly hinders their broad clinical application. Besides their ability to differentiate into different tissue types, stem cells may contribute to tissue regeneration through the secretion of paracrine factors. Here we examined the potential for using a minimal number of NChons to catalyze cartilage tissue formation by co-culturing them with adipose-derived stem cells (ADSCs) in 3D biomimetic hydrogels.


N. Harada Y. Watanabe S. Abe K. Sato T. Iwai I. Yamamoto K. Yamada K. Yamanaka Y. Sakai T. Kaneko T. Matsushita

Introduction

Mesenchymal stem cells (MSCs) are identified by having the ability to differentiate into various tissues and typically used to generate bone tissue by a process of resembling intramembranous ossification, namely by direct osteoblastic differentiation. However, most bones develop by endochondral ossification, namely via remodeling of hypertrophic cartilaginous templates. To date, reconstruction of bone defects by endochondral ossification using mesenchymal stem cell-derived chondrocytes (MSC-DCs) have not been reported. The purpose of this study was to evaluate the effects of the transplantation of MSC-DCs on bone healing in segmental defects in rat femurs.

Methods

Segmental bone defects (5, 10, 15-millimeter) were produced in the mid-shaft of the femur of the Fisher 344 rats and stabilised with an external fixator. Bone marrow was aspirated from the rat's femur and tibia at 4 weeks before operation. MSCs were isolated and grown in culture and seeded on a Poly dl-lactic-co glycolic acid (PLGA) scaffold. Subsequently, the scaffold was cultured using chondrogenic inducing medium for 21 days. The characteristics of the PLGA scaffold are radiolucent and to be absorbed in about 4 months. The Treatment Group received MSC-DCs, seeded on a PLGA scaffold, locally at the site of the bone defect, and Control Group received scaffold only. The healing processes were monitored radiographically and studied biomechanically and histologically.


T. Grossner U. Haberkorn T. Gotterbarm

Summary Statement

One of the most challenging problems in osteogenic 3D-tissue engineering is, to quantify the amount of new hydroxylapatite deposition. 18F-NaF-Labeling is a new, high-sensitive method to proof and quantify the osteogenic potential of hMSCs in an in vitro 3D-model.

Introduction

18F-labeled sodium fluorine was the first widely used agent for skeletal scintigraphy in the 1960s. 18F-NaF is rapidly exchanged for hydroxylgroups of the hydroxylapatite, covalently binding to the surface of new bone, which results in the formation of fluoroapatite. Three dimensional scaffolds are used to favor osteogenic differentiation of precursor cells. Cell-loaded scaffolds are investigated for their healing potential of critical size bone defects. Assessing the osteogenic potential of MSCs in 3D-in vitro cultures is of major interest in tissue engineering in order to maximise bone formation in vitro and in vivo.

One of the most challenging problems is, to quantify directly the amount of new hydroxylapatite deposition without destroying the evaluated cell-loaded scaffold. Within this abstract, we present a novel, non-destructive, high-sensitive method to quantify the amount of local hydroxylapatite deposition in 3D-cultures using 18F-NaF.


M. Manassero V. Viateau A. Decambron M. Deschepper M. Bensidhoum D. Logeart H. Petite

Summary

Despite similar, early and massive death, hMSCs promote bone formation which was higher in orthotopic than ectopic site suggesting a trophic effect of hMSCs. Ectopic implantation is suitable to evaluate cell survival, but assessment of bone formation requires orthotopic implantation

Introduction

Tissue constructs containing mesenchymal stem cells (MSCs) are appealing strategies for repairing large segmental bone defects but they do not allow consistent bone healing and early and massive MSCs death was identified as a cause of failure. However, little is known about cell survival in the clinical micro-environment encountered during bone healing process, whereas ectopic evaluation is well documented.

In vivo, luciferase-labelled human MSCs survival, within osteoconductive scaffold, was compared in orthotopic and ectopic locations, and bone formation ability of LF-hMSCs-Acropora constructs was evaluated. Interest and limits of each model were highlighted.


G.M. de Peppo I. Marcos-Campos D. Kahler D. Alsalman L. Shang G. Vunjak-Novakovic D. Marolt

Summary Statement

A biomimetic tissue engineering strategy involving culture on bone scaffolds in perfusion bioreactors allows the construction of stable, viable, patient-specific bone-like substitutes from human induced pluripotent stem cells.

Introduction

Tissue engineering of viable bone substitutes represents a promising therapeutic strategy to mitigate the burden of bone deficiencies. Human induced pluripotent stem cells (hiPSCs) have an excellent proliferation and differentiation capacity, and represent an unprecedented resource for engineering of autologous tissue grafts, as well as advanced tissue models for biological studies and drug discovery. A major challenge is to reproducibly expand, differentiate and organize hiPSCs into mature, stable tissue structures. Based on previous studies (1,2,3), we hypothesised that the culture conditions supporting bone tissue formation from adult human mesenchymal stem cells (hMSCs) and human embryonic stem cell (hESC)-derived mesenchymal progenitors could be translated to hiPSC-derived mesenchymal progenitors. Our objectives were to: 1. Derive and characterise mesenchymal progenitors from hiPSC lines. 2. Engineer bone substitutes from progenitor lines exhibiting osteogenic potential in an osteoconductive scaffold – perfusion bioreactor culture model. 3. Assess the molecular changes associated with the culture of hiPSC-progenitors in perfusion bioreactors, and evaluate the stability of engineered bone tissue substitutes in vivo.


K. Trieb G. Pass S. Hofstaetter

Summary Statement

Treatment of non-union is a highly demanding field with respect to bone healing. BMP 7 is a useful, wide-ranged tool in treating non-union of the foot and benign bone tumors. It represents a low-risk procedure with a high level of reliability.

Introduction

Treatment of non-union is a highly demanding field with respect to bone healing. Treatment of tibial fracture non-union with the bone morphogenetic protein 7 (BMP-7) has been successfully reported. BMP 7 is a recombinant human protein produced in ovary cells of the Chinese hamster. It is responsible for the differentiation of mesenchymal stem cells from the periost, muscle and sponious bone and stimulates bone formation. It is the aim of our study to investigate the use of BMP 7 for other locations than the tibia, such as the foot and benign bone tumors. We strive for union or revision in each medical case.


F. Taddei I. Palmadori E. Schileo M.O. Heller W.R. Taylor A. Toni

Summary Statement

A population based finite element study that accounts for subject-specific morphology, density and load variations, suggests that osteoporosis does not markedly lower the mechanical compliance of the proximal femur to routine loads.

Introduction

Osteoporosis (OP) is a bone disease defined by low bone density and micro-architectural deterioration. This deterioration is neither uniform nor symmetric at the proximal femur. Evidence from analyses performed at the tissue level suggests that the cortical shell at the femoral neck is thinner in OP patients, especially in the superior regions, but not in the infero-anterior ones [Poole, Rubinacci]. Analogously, OP femurs show a higher anisotropy of the trabecular bone than controls [Ciarelli], suggesting a preservation of load bearing capacity in the principal loading direction vs. the transverse one. There is general consensus that the regions subjected to higher loads during walking, which is the predominant motor activity in the elderly, are mostly preserved. All these findings suggest that the OP femur should exhibit an almost normal mechanical competence during daily activities. This would be in accordance with the very low incidence of spontaneous fractures [Parker] and with the moderate fracture predictivity of BMD. Although reasonable, this hypothesis has never been tested at the organ level. Aim of the present study was to verify it with a population-based finite element (FE) study.


N. Brandolini N. Kapur R.M. Hall

Summary Statement

Burst fractures were simulated in vitro on human cadaveric spine segments. Displacement of the facet joints and pedicles were measured throughout the fracture process showing how these bony structures behave when an impact load is delivered.

Introduction

Burst fractures account for almost 30% of all spinal injuries, which may result in severe neurological deficit, spinal instability and hence life impairment1. The onset of the fracture is usually traumatic, caused by a high-energy impact loading. Comminution of the endplates and vertebral body, retropulsion of fragments within the canal and increase of the intrapedicular distance are typical indicators of the injury. Experimental and numerical studies have reported strain concentration at the base of the pedicles, suggesting that the posterior processes play a fundamental role in the fracture initiation2,3. However, little is known about the dynamic behaviour of the vertebra undergoing an impact load. The aim of this study was to provide an in vitro cadaveric investigation on burst fracture, focusing on the widening of the facet joints and pedicles during the fracture development.


G. Farinella M. Viceconti E. Schileo C. Falcinelli L. Yang R. Eastell

Summary

A retrospective study on 98 patients shows that FE-based bone strength from CT data (using validated FE models) is a suitable candidate to discriminate fractured versus controls within a clinical cohort.

Introduction

Subject-specific Finite element models (FEM) from CT data are a promising tool to non-invasively assess the bone strength and the risk of fracture of bones in vivo in individual patients. The current clinical indicators, based on the epidemiological models like the FRAX tool, give limitation estimation of the risk of femoral neck fracture and they do not account for the mechanical determinants of the fracture. Aim of the present study is to prove the better predictive accuracy of individualised computer models based a CT-FEM protocol, with the accuracy of a widely used standard of care, the FRAX risk indicator.


S. Thakkar E. Langdale S. Mears S. Belkoff

Summary

A rotational limit for screw insertion may improve screw purchase and plate compression by reducing stripping, as compared to a torque based limit.

Introduction

Over-tightening screws results in inadvertent stripping of 20% of cortical bone screws. The current method of “two-fingers tight” to insert screws relies on the surgeon receiving torque feedback. Torque, however, can be affected by screw pitch, bone density and bone-thread friction. An alternative method of tightening screws is the “turn-of-the-nut” model, commonly used in engineering applications. In the “turn-of-the-nut” method, nuts used to fasten a joint are rotated a specific amount in order to achieve a pre-specified bolt tension. When applied to orthopaedics, bone assumes the role of the nut and the screw is the bolt. The screw is turned a set angular rotation that is independent of torque feedback. Potentially the “turn-of-the-nut” method provides an easier way of screw insertion that might lessen inadvertent screw stripping. The purpose of the current study was to use the “turn-of-the-nut” method to determine the angular rotation that results in peak plate compression and peak screw pullout force.


K. Kojima M. Lenz T. Nicolino G. Hofmann R.G. Richards B. Gueorguiev

Summary Statement

Tibia plateau split fracture fixation with two cancellous screws is particularly suitable for non-osteoporotic bone, whereas four cortical lag screws provide a comparable compression in both non-osteoporotic and osteoporotic bone. Angle-stable locking plates maintain the preliminary compression applied by a reduction clamp.

Introduction

Interfragmentary compression in tibia plateau split fracture fixation is necessary to maintain anatomical reduction and avoid post-traumatic widening of the plateau. However, its amount depends on the applied fixation technique. The aim of the current study was to quantify the interfragmentary compression generated by a reduction clamp with subsequent angle-stable locking plate fixation in an osteoporotic and non-osteoporotic synthetic human bone model in comparison to cancellous or cortical lag screw fixation.


L. Sudre M. Cruel P. Becquart T. Hoc H. Petite M. Bensidhoum

Summary

Shear stress and hydrostatic effects on the hMSCs early mechano gene response were similar. For the same magnitude gene response, the hydrostatic compression (1.5×105 Pascal) is a 200000 times greater than the force exerted by shear stress (0.7 Pascal).

Introduction

In the lab, a perfusion bioreactor designed to automate the production of bone constructs was developed. The proof of concept was established in a large animal model of clinical relevance. The cells perfused in the bioreactor are likely to perceive 2 types of stresses: shear stress and hydrostatic pressure. Optimization of this bioreactor implies a better understanding of the effects of these forces on the cells in order to have better proliferation and differentiation. An understanding of the response of one cell layer submit to various strength is relevant. The primary objective of this study was to test the hypothesis that hMSCs have the fundamental ability to distinguish between different types of mechanical signals as evidenced by distinct gene expression. The effect of shear stress on one cell layer cultures of hMSCs will be evaluated using a commercially available system called Ibidi. For the hydrostatic pressure as there is no commercial device available, our group has developed a prototype capable of delivering a well-defined mechanical loading to cells in culture.

Validation of the techniques: In order to validate the systems (shear stress and cyclic pressure apparatus) used in this study, we have used an osteocytes-like cell line, MLO-Y4. When stimulated by a 30 minutes PFF at 7 dyn/cm2 or hydrostatic compression at 1.5 bar, cells responded by producing NO in the culture media

NO release after mechanical stimulation of hMSCs: hMSCs were subjected to increased PFF (7 to 42 dyn/cm2) for 30 minutes. This stimulation resulted in an increased release of NO in the media compared to non-stimulated cells (p<0.05). Interestingly the level of NO was maximal at 7 dyn/cm2 and decreased with higher flow rate. Similar observation was made after hMSCs stimulation by hydrostatic pressure for 30 minutes: a peak of NO release at 1.5 bar was observed

Early gene expression of known mechano-sensitive genes: Gene expression analysis immediately after stimulation (PFF or hydrostatic compression) was performed on a range of known mechano-sensitive genes: NOS2, PTGS2, PTGES, IER3 and EGR1. Immediately after stimulation by PFF at 7 dyn/cm2 or hydrostatic pressure at 1.5 bars, the expression of all the genes of interest appear to be up regulated in stimulated cells


S.Y. Jauch G. Huber K. Sellenschloh H. Haschke T.M. Grupp M.M. Morlock

Summary

Micromotions between stem and neck adapter depend on prosthesis design and material coupling. Based on the results of this study, the amount of micromotion seems to reflect the risk of fretting-induced fatigue in vivo.

Introduction

Bimodular hip prostheses were developed to allow surgeons an individual reconstruction of the hip joint by varying length, offset and anteversion in the operation theatre. Despite these advantages, the use of these systems led to a high rate of postoperative complications resulting in revision rates of up to 11% ten years after surgical intervention. During daily activities taper connections of modular hip implants are highly stressed regions and contain the potential of micromotions between adjacent components, fretting and corrosion. This might explain why an elevated number of fretting-induced neck fractures occurred in clinics. However, some bi-modular prostheses (e.g. Metha, Aesculap, Ti-Ti) are more often affected by those complications than others (e.g. H-Max M, Limacorporate, Ti-Ti or Metha, Ti-CoCr) implying that the design and the material coupling have an impact on this failure pattern. Therefore, the purpose of this study was to clarify whether clinical successful prostheses offer lower micromotions than those with an elevated number of in vivo fractures.


S.Y. Jauch L.V. Ng S.R. Peirce V. Dhokia A.W. Miles H.S. Gill

Summary

The required torque leading to an abrasion of the passive layer in the stem-head interface positively correlates to the assembly force. In order to limit the risk of fretting and corrosion a strong hammer blow seems to be necessary.

Introduction

Modular hip prostheses are commonly used in orthopaedic surgery and offer a taper connection between stem and ball head. Taper connections are exposed to high bending loads and bear the risk of fretting and corrosion, as observed in clinical applications. This is particularly a problem for large diameter metal bearings as the negative effects may be enhanced due to the higher moments within the taper connection. Currently, it is not known how much torque is required to initiate a removal of the passive layer, which might lead to corrosion over a longer period and limits the lifetime of prostheses. Therefore, the purpose of this study was to identify the amount of torque required to start an abrasion of the passive layer within the interface dependent on the assembly force and the axial load.


A. Kinbrum A. Traynor S. Collins

Summary

This work uses a mathematical method to correlate the forces calculated to push-on and pull off a femoral head from a stem and correlate the results of in vitro testing.

Introduction

This work aimed to mathematically model the force needed to disassemble the THR unit for a given assembly load. This work then compared these results with the results of an in vitro experiment. The research presented aimed to determine the assembly forces necessary to prevent movement of the head on the stem through friction. By assessing the forces necessary to push the head onto the stem securely enough to prevent any movement of the head through friction, it is likely that the fretting and corrosion of the head taper interface will be reduced.


N. Sasaki K. Farraro K. Kim S. Woo

Summary Statement

ACL reconstruction using a quadriceps tendon autograft was quantitatively evaluated using a robotic testing system. Biomechanical results on joint stability and graft function support its use as an alternative to the hamstrings.

Introduction

Recently, a number of surgeons have chosen the quadriceps tendon (QT) autograft as an alternative autograft over the hamstrings tendon for ACL reconstruction because its bone-to-bone healing on one side, large size, and preservation of lateral and rotatory knee function could lead to fewer post-operative complications. However, there have been little or no biomechanical studies that quantitatively evaluate knee function after reconstruction using a QT autograft. Therefore, the objective of this study was to assess the function of a reconstructed knee with a QT autograft and compare the results with a quadrupled semitendinosus and gracilis (QSTG) tendon autograft on the same knee.


A. Bistolfi P. Bracco G. Banche V. Allizond M. Boffano A. Cimino E.M. Brach del Prever A.M. Cuffini

Summary

Prosthetic UHMWPE added with vitamin E and crosslinked UHMWPE are able to decrease significantly the adhesion of various bacterial and fungal strains limiting biomaterial associated infection and consequent implant failure.

Introduction

Polyethylene abrasive and oxidative wear induces overtime in vivo a foreign-body response and consequently osteolysis, pain and need of implant revision. To solve these problems the orthopaedic research has been addressed to develop new biomaterials such as a crosslinked polyethylene with a higher molecular mass than standard Ultra High Molecular Weight Polyethylene (UHMWPE), and consequently a higher abrasive wear resistance and an antioxidant (vitamin E)-added UHMWPE to avoid oxidative wear. Nevertheless a feared complication of implant surgery is bacterial or fungal infection, initiated by microbial adhesion and biofilm formation, and related to the biomaterial surface characteristics. Staphylococci are the most common microorganisms causing biomaterial associated infection (BAI), followed by streptococci, Gram-negative bacilli and yeasts. With the aim to prevent BAI, the purpose of this study was to evaluate the adhesion of various microbial strains on different prosthetic materials with specific surface chemical characteristics, used in orthopaedic surgery.


G. Del-Prado F.-J. Pascual A. Terriza D. Molina-Manso F. Yubero J.-A. Puertolas E. Gomez-Barren J. Esteban

Summary Statement

A study to evaluate biofilm development on different coatings of UHMWPE was performed. We observed a species-specific effect, with S. aureus affected mainly by DLC-F and S. epidermidis by DLC. These data correlates with previous adherence studies.

Introduction

Prosthetic joint infection is intimately related to bacterial biofilms on implant biomaterials. Recently, diamond-like carbon (DLC) coating has been suggested to improve the antibacterial performance of medical grade GUR1050 ultra high molecular weight polyethylene (UHMWPE) supplied by Orthoplastics bacup, UK versus collection and clinical staphylococcal strains. The aim of this study was to make an approximation towards the actual impact of such coatings in biofilm formation.


N. Russell R. Oliver W. Walsh

Summary Statement

Supercritical fluid (SCF) sterilization produces clean and osteoconductive allograft bone capable of healing a critical-sised bony defect. SCF treated graft induces an increased anabolic response and decreased catabolic reponse compared to gamma irradiated graft.

Introduction

Clinically, allogeneic bone graft is used extensively because it avoids the donor site morbidity associated with autograft. However, there are concerns over the optimal sterilization method to eliminate immunological risks whilst maintaining the biological efficacy of the graft. This study compared the effect of Supercritical fluid (SCF) sterilization and gamma irradiation on the osteoconductivity of allograft bone in a bilateral critical-sised defect rabbit model.


S. Spriano S. Ferraris M. Miola

Summary Statement

The problem facing this research is to promote rapid osteointegration of titanium implants and to minimise the risks of infections by the functionalization with different agents, each designed for a specific action. A patented process gives a multifunctional titanium surface.

Introduction

A patented process of surface modification is described. It gives a multifunctional surface with a multiscale roughness (micro and nano topography), that is excellent for osteoblast adhesion and differentiation. It has a high degree of hydroxylation, that is relevant for inorganic bioactivity (apatite-HA precipitation) and it is ready for a functionalization with biological factors. A direct grafting of ALP has been obtained. Moreover, the growth of an antibacterial agent within the surface oxide layer can be useful in order to combine the osteoinduction ability to antimicrobial effects. The selection of an inorganic agent (metal nanoparticles) has the advantage to avoid an eventual development of antibiotic resistance by bacteria.


M. Bianchi E. Urquia Edreira J. Wolke Z. Tahmasebi Birgani P. Habibovi A. Tampieri J.A. Jansen M. Marcacci S.C.G. Leeuwenburg J.J.J.P. van den Beucken

Summary Statement

Repetitive concavities threaded on the surface of bone implants have been already demonstrated to be effective on ectopic bone formation in vivo. The aim of this study was to investigate the effect of concavity on the mineralization process in vitro.

Introduction

The role of implant surface geometry in bone formation has been extensively investigated. Ripamonti and co. investigated the possibility to induce bone formation by threading concavities on the surface of calcium phosphate implants, without the need for exogenous osteogenic soluble factors. The underlying hypothesis was that this geometry, by resembling the hemi-osteon trench observable during osteoclastogenesis, was able to activate the ripple-like cascade of bone tissue induction and morphogenesis. Despite several studies indicating a positive effect of concavities on bone induction, so far no attempts have rationalised this phenomenon by means of in vitro tests. Consequently, this study aimed to evaluate the effect of surface concavities on the mineralization of hydroxyapatite (HA) and beta-tricalciumphosphate (b-TCP) ceramics in vitro. Our hypothesis was that concavities could effectively guide the mineralization process in vitro.


S. Ray

Summary Statement

The present study demonstrates the beneficial effects of strontium (Sr) modified calcium phosphate cement to improve new bone formation in a metaphyseal osteoporotic fracture defects in rats compared to calcium phosphate cement and empty defects. Keywords: strontium, fracture, calcium phosphate, bone formation

Introduction

Impaired fracture healing with subsequent implant failure is a dramatic problem in osteoporotic fractures. Biomaterials are of interest to stimulate fracture healing in osteoporotic defects and the objective of the current study is to investigate the effects of Strontium modified calcium phosphate cement (SrCPC) in a critical-size metaphyseal fracture defect of osteoporotic rats compared to calcium phosphate (CPC) and empty defect control group.


P. Arntz M. Kuhli N. Reimers H. Steckel

Summary Statement

This work features a new approach to overcome drawbacks of commercial calcium phosphate cements in terms of application by on-site preparation and bone ingrowth by introduction of macropores in the material using a hydrofluoroalkane based aerosol foam.

Introduction

The application of calcium phosphate bone cements (CPCs) into a void for example of an osteoporotic bone is very difficult as the cement paste is made outside the application site and subsequently applied into the damaged bone. A common drawback of especially apatitic cements is a very low resorption rate due to small pore size Therefore different approaches have been described to add macropores into the cement2, leading to bone ingrowth and tissue penetration. The aim of this project is the use of two separate formulations in pressurised systems – a suspension and an emulsion – which can be mixed in a specially developed device and can be applied easily and efficiently into a bone directly during surgery leading to a self-hardening macro porous CPC foam. The intention is to fill voids in osteoporotic bones to ensure stability for implants like e.g. screws for femur neck fractures. An increased stability for implants can allow the possibility of a less invasive femur neck preserving therapy in contrast to a femur neck replacement. Other indications for such foam (i.e. kyphoplasty) are under evaluation.


D. Logeart-Avramoglou R. Guillot P. Becquart F. Gilde F. Sailhan A. Lapeyre C. Picart

Summary

Coating of titanium implants with BMP-2-loaded polyelectrolyte multilayer films conferred the implant surface with osteoinductive properties which are fully preserved upon both air-dried storage and γ-sterilization.

Although BMP-2 is recognised as an important molecule for bone regeneration, its supraphysiological doses currently used in clinical practice has raised serious concerns about cost-effectiveness and safety issues. Thus, there is a strong motivation to engineer new delivery systems or to provide already approved materials with new functionalities. Immobilizing the growth factor onto the surface of implants would reduce protein diffusion and increase residence time at the implantation site. To date, modifying the surfaces of metal materials, such as titanium or titanium alloys, at the nanometer scale for achieving dependable, consistent and long-term osseointegration remains a challenging approach.

In this context, we have developed an osteoinductive coating of a porous titanium implant using biomimetic polyelectrolyte multilayer (PEM) films used as carriers of BMP-2. The PEM films were prepared by alternate deposition of 24 layer pairs of poly(L-lysine) (PLL) and hyaluronic acid (HA) layers (∼3.5 µm in thickness); such films were then cross-linked by means of a water-soluble carbodiimide (EDC) at different degrees. The amount of BMP-2 loaded in these films was tuned (ranging from 1.4 to 14.3 µg/cm2) depending on the cross-linking extent of the film and of the BMP-2 initial concentration. Because packaging, and storage of the devices are important issues that may limit a wide application of biologically functionalised materials, we assessed in the present study the osteoinductive performance of the BMP-2 loaded PEM coatings onto custom-made 3D porous scaffolds made of Ti-6Al-4V in vitro and in vivo pertinent to long-term storage in a dry state and to sterilization by gamma irradiation.

Analysis of PEM films by infrared spectroscopy evidenced that the air-dried films were stable for at least one year of storage at 4°C and they resisted exposure to γ-irradiation at clinically approved doses. The preservation of the growth factor bioactivity was evaluated both in vitro (using C2C12 cell model) and in vivo (in a rat ectopic model). In vitro, BMP-2 loaded in dried PEM films exhibited shelf-life stability at 4°C over a one-year period. However, its bioactivity decreased from 50 to 80% after γ-irradiation at 25 and 50 kGy, respectively. Remarkably, the in vivo studies showed that the amount of new bone tissue formation induced by BMP-2 contained in PEM-coated Ti implants was not affected after air-drying of the implants and sterilization at 25 kGy indicating the full preservation of the growth factor bioactivity.

Altogether, our results provided evidence of the remarkable property of PEM film coatings that both sequester BMP-2 and preserve its full in vivo osteoinductive potential upon both storage and γ-sterilization. The protective effects of PEM films on the growth factor bioactivity may be attributed to both the high water content in (PLL/HA) films (∼90%) and to their porosity, which may provide a “protein-friendly” environment similar to the natural extracellular matrix. This novel “off-the-shelf” technology of functionalised implants opens promising applications in prosthetic and tissue engineering fields.


R. Dowling C. Pendegrass B. Thomas G. Blunn

Summary

Osseointegrated Amputation Prostheses can be functionalised by both biological augmentation and structural augmentation. These augmentation techniques may aid the formation of a stable skin-implant interface.

Introduction

Current clinical options are limited in restoring function to amputees, and are associated with contact dermatitis and infection at the stump-socket interface. Osseointegrated Amputation Prosthesis attempts to solve issues at the stump-socket interface by directly transferring axial load to the prosthesis, via a skin-penetrating abutment. However, development is needed to achieve a seal at the skin-implant interface to limit infection. Fibronectin, an Extracellular Matrix protein, binds to integrins during wound healing, with the RGD tripeptide being part of the recognition sequence for its integrin binding domain. In vitro work has found silanization of RGD to polished titanium discs up regulates fibroblast attachment compared to polished control. Electron Beam Melting can produce porous titanium alloy implants, which may encourage tissue attachment. This study aims to test whether a combination of biological RGD coatings and porous metal manufacturing techniques can encourage the formation of a seal at the skin-implant interface.


H.M. Wong P. Chu K. Cheung K. Luk K. Yeung

Summary

A promising approach to stimulate in vivo bone formation by using our newly developed magnesium-based bone substitutes, which can be an alternative to treat the patients with bone loss in addition to the anticatabolic drugs and growth factors.

Introduction

Bone impairment arising from osteoporosis as well as other pathological diseases is a major health problem. Anti-catabolic drugs such as bisphosphonates and other biological agents such as bone morphogenetic proteins and insulin-like growth factor can theoretically apply to stimulate bone formation. However, the formation of more brittle bone and uncontrolled release rate are still a challenge nowadays. Hence, we propose to stimulate bone formation by using a newly developed magnesium-based bone substitute. Indeed, the presence of magnesium ions can stimulate bone growth and healing by enhancing osteoblastic activity. This study aims to investigate the mechanical, in vitro and in vivo properties of this novel bone substitute.


C. Egloff R. Serrattan D. Hart A. Sawatsky T. Leonard V. Valderrabano W. Herzog

Summary Statement

We observed that severe muscle weakness leads to OA, whereas a transient inflammatory stimulus did not have a significant effect on cartilage degradation. This arises the thought that a severe but transient inflammation may not be an independent risk factor for OA.

Introduction

Biomechanical disturbances and joint inflammation are known risk factors, which may provoke or advance osteoarthritis (OA). However, the effect of interactions of such risk factors on the onset and progression of OA are still poorly understood. Therefore, the goal of this study was to investigate the in vivo effects of muscle weakness, joint inflammation, and the combination of these two risk factors, on the onset and progression of OA in the rabbit knee.


P. Gauthier D. Benoit

Summary

This study describes the use of a quasi-static, 6DOF knee loading simulator using cadaveric specimens. Muscle force profiles yield repeatable results. Intra-articular pressure and contact area are dependent on loading condition and ACL integrity.

Introduction

Abnormal contact mechanics of the tibiofemoral joint is believed to influence the development and progression of joint derangements. As such, understanding the factors that regulate joint stability may provide insight into the underlying injury mechanisms. Muscle action is believed to be the most important factor since it is the only dynamic regulator of joint stability. Furthermore, abnormal muscle control has been experimentally linked to the development of OA [Herzog, 2007] and in vivo ACL strain [Fleming, 2001]. However, the individual contributions to knee joint contact mechanics remain unclear. Thus, the purpose of this study was to examine the effects of individual muscle contributions on the tibiofemoral contact mechanics using an in-vitro experimental protocol.


C. Florea M.K.H. Malo J. Rautiainen J.T.A. Mäkelä M.T. Nieminen J.S. Jurvelin A. Davidescu R.K. Korhonen

Summary

In a rabbit model of early osteoarthritis, structural changes in femoral condyle cartilage were severer in the lateral compartment and preceded alterations in the underlying bone. In the medial compartment, altered bone properties occurred together with structural changes in cartilage.

Introduction

Early osteoarthritic changes in cartilage have been previously studied through anterior cruciate ligament transection (ACLT) in rabbits. However, parallel changes in the structure of subchondral and trabecular bone at 4 weeks after ACLT are not known.


J. Geurts A. Patel U. Helmrich M. Hirschmann M. Müller-Gerbl V. Valderrabano T. Hügle

Summary Statement

Cross-talk between cells from immune and bone system might play a role in molecular regulation of subchondral bone sclerosis in osteoarthritis. Macrophages, B-lymphocytes and tartrate-resistant acid phosphatase activity are specifically increased in sclerotic subchondral bone of patients with knee osteoarthritis.

Background

Recent investigations have provided substantial evidence that distinct molecular and morphological changes in subchondral bone tissue, most notably sclerosis, play an active and important role in the pathogenesis of OA. The cellular and molecular regulation of this pathological process remains poorly understood. Here, we investigated whether osteoimmunology, the reciprocal signaling between cells from the immune and bone system, is involved in OA subchondral bone sclerosis.


C. Wen K. Wong C. Liu C. Yan W. Lu K.Y. Chiu

Summary Statement

OA knee with subchondral cyst formation presented differential microstructure and mechanical competence of trabecular bone. This finding sheds light on the pivot role of subchondral cyst in OA bone pathophysiology.

Introduction

Subchondral bone cyst (SBC) is a major radiological finding in knee osteoarthritis (OA), together with joint space narrowing, osteophyte and sclerotic bone formation. There is mounting evidence showing that SBC originates in the same region as bone marrow lesions (BMLs). The presence of subchondral bone cyst (SBCs), in conjunction with BMLs, was associated with the severity of pain, and was able to predict tibial cartilage lolume loss and risk of joint replacement surgery in knee OA patient. It is speculated that the presence of SBCs might increase intraosseous pressure of subchondral bone, and trigger active remodeling and high turnover of surrounding trabecular bone. Yet the exact effect of SBC on the structural and mechanical properties trabecular bone, which provides the support to overlying articular cartilage, remains to be elucidated. Therefore, this study aimed to investiate the microstructure and mechanical competence of trabecular bone of knee OA in presence or absence of SBC.


A. Palmer S. Fernquest L. Hamish T. Pollard E. McNally D. Wilson D. Wilson B. Madler A. Carr S. Glyn-Jones

Summary

The dGEMRIC index correlates more strongly with the pattern of radiographic joint space narrowing in hip osteoarthritis at five year follow-up than morphological measurements of the proximal femur. It therefore offers potential to refine predictive models of hip osteoarthritis progression.

Introduction

Longitudinal general population studies have shown that femoroacetabular impingement increases the risk of developing hip osteoarthritis, however, morphological parameters have a low positive predictive value. Arthroscopic debridement of impingement lesions has been proposed as a potential strategy for the prevention of osteoarthritis, however, the development of such strategies requires the identification of individuals at high risk of disease progression. We investigated whether delayed Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) predicts disease progression. This imaging modality is an indirect measure of cartilage glycosaminoglycan content.


E. Morsi T. Eid M. Hadhoud A. Elseedy

Summary Statement

This work proved by prospective clinical and radiological controlled study that the best regimen for treatment of early KOA is combination of NSAIDS, physiotherapy, vasoprotective and vasodilator drugs, and alendronate.

Introduction

There is controversy in the literatures regarding the best treatment for early knee osteoarthritis because there is a more controversy regarding the initiating factor of KOA The Objectives of this work were to evaluate the efficacy of various treatment regimens for the prevention of progression of early knee osteoarthritis (KOA). Also, to elucidate the factors for initiation and progression of KOA


M. Smith A. Schiavinato C. Little

Introduction

Osteoarthritis (OA) involves pathological change in all joint tissues, including cartilage degradation and synovitis. Synovial inflammation is significantly associated with pain severity and incidence in knee OA. It is becoming evident that synovitis also plays an active role in the initiation and progression of cartilage erosion in OA, through direct secretion of catabolic enzymes as well as factors that stimulate chondrocyte catabolic activity. Therapeutic agents that target both synovitis and cartilage pathology are likely to be maximally beneficial in treating pain and slowing cartilage breakdown in OA. We have previously shown that an amide-derivative of HA (HYMOVIS™) was superior to native HA of the same MW in improving gait, and reducing synovial hyperplasia in a sheep OA model. In the present study the mechanisms whereby the chemically modified HA may be beneficial were examined using chondrocytes and synovial fibroblasts from knees of OA patients.

Patients & Methods

Chondrocytes (HAC, n=6) and synovial fibroblasts (HSF, n=6) were isolated from OA patients at the time of knee replacement. HYMOVIS™ (0, 0.5, 1.0 or 1.5mg/mL) was added to simultaneously or 1 hour before interleukin-1β (IL1, 2ng/mL). Cultures were terminated 30 minutes later for Bioplex® quantitation of p-JNK, p-NFκB and p-p38; or 24 hours later for RNA isolation and analysis of gene expression by real time RT-PCR, and measurement of MMP13 activity in the media. Only statistically significant results are reported.


L. Harrold D. Ayers G. Reed P. Franklin

Summary Statement

For RA patients undergoing TKR, the gain in function at 6 months following surgery is less than that experienced by OA patients; for THR, however, gains are similar in OA and RA patients.

Introduction

Total joint replacement (TJR) is commonly used in rheumatoid arthritis (RA) patients and yet little information is available to quantify their functional gain following surgery and how it differs from what the osteoarthritis (OA) population experiences. Therefore, we examined 6-month functional outcomes of TJR in a population-based observational cohort of RA and OA patients who underwent total hip (THR) or knee (TKR) replacement.


H. Chang D. Docheva U. Knothe M.L. Knothe Tate

Summary Statement

Progenitor cells from the periosteal niche are of great clinical interest due to their remarkable regenerative capacity. Here we report on progenitor cells from arthritic patients whose femoral neck periosteum was resected over the course of hip replacement.

Introduction

This study aims to determine whether periosteum derived cells (PDCs) can be isolated from tissue resected in the normal course of hip arthroplasty. Further, it aims to determine how different isolation protocols affect PDC behavior (surface marker expression, proliferation, and differentiation). In addition, the study aims to characterise the populations of PDCs, isolated through either enzymatic digestion or migration, and their relative capacity to differentiate down multiple capacities; direct comparison with commercially available human marrow-derived stromal cells cultured under identical conditions will enable the placement of the PDC data in context of the current state of the field.


S Avnet M Salerno N Zini D Gibellini N Baldini

Summary

We demonstrate that osteoclast-like cells of GCT result from the spontaneous fusion and differentiation of CD14+ cells of the monoblastic lineage by an autocrine mechanism mediated by RANKL, rather than induced by stromal cells. This process is further enhanced by the simultaneous impairment of the negative feed-back regulation of osteoclastogenesis by interferon β.

Introduction

Giant cell tumor of bone (GCT) is a benign osteolytic lesion with a complex histology, comprising prominent multinucleated osteoclast-like cells (OC), mononuclear stromal cells (SC), and monocyte-like elements. So far, most studies have focused on SC as the truly transformed elements that sustain osteoclast differentiation, while less attention has been paid on the monocyte-like cell fraction. On the contrary, we have previously shown that SC are non-transformed element that can induce osteoclastogenesis of monocytes at levels that do not exceed that of normal mesenchymal stromal cells. We therefore focused on CD14+ monocyte-like cells as an alternative key candidate for the pathogenesis of GCT.


V. Sollazzo

Summary Statement

In this study we suggested a possible role of prion proteins genes in osteosarcoma. Therefore, the inhibition of prion proteins expression must be tested because it could represent a new approach to the molecular treatment of osteosarcoma.

Introduction

Although osteosarcoma is the most common bone malignancy, the molecular and cellular mechanisms influencing its pathogenesis have remained elusive. Prion proteins (PRNP and PRND), known mostly for its involvement in neurodegenerative spongiform encephalopathies, have been recently demonstrated to be involved in resistance to apoptosis, tumorigenesis, proliferation and metastasis.


G. Bonuccelli S. Avnet C. Fotia M. Salerno G. Grisendi D. Granchi M. Dominici N. Baldini

Summary

Reciprocal metabolic reprogramming of MSCs and osteosarcoma cells influences tumor-stroma cross talk. Drugs targeting Warburg metabolism may define innovative therapeutic approaches in osteosarcoma.

Introduction

Osteosarcoma (OS) is a malignant primary bone tumour of mesenchymal origin, in which cells with stem-like characteristics (CSCs) have been described. Recent studies have demonstrated a mutual interaction between stroma and tumor cells in exploiting a role in the pathogenesis and progression of cancer, and also in the enhancing stemness phenotype. Here we take in consideration the complex juxtacrine and paracrine intercellular cross talk played by mesenchymal stromal cells (MSCs) with adherent osteosarcoma cells and OS cells with stem-like characteristics (CSCs).


M. Salerno S. Avnet G. Bonuccelli A. Eramo R. De Maria M. Gambarotti G. Gamberi N. Baldini

Summary

Starting from human musculoskeletal sarcomas, we isolated a subset of cells that display cancer stem cell properties. The control of culture conditions is crucial to enhance the isolation of this cell population.

Introduction

Cancer stem cells (CSCs) have emerged as the real responsible for the development, chemoresistance, and metastatic spread of different human cancers, including musculoskeletal sarcomas. However, unlike most leukemias and solid tumors, so far, data on musculoskeletal sarcomas refer to CSCs obtained from established cell lines, and only a few authors have reported on the isolation of CSCs from tissue samples [1-7]. Reasonably due to some peculiar features of mesenchymal tumors, including the lack of unique surface markers that identify tumor progenitors, there are still partial clues on the existence of a CSC population in these cancers. Here, we report the identification of putative CSCs in musculoskeletal sarcomas using the most general accepted isolation method, the sphere culture system. Accordingly to recent reports, we also analyzed the effects of reduced oxygen availability on the behavior of sarcoma CSCs.


M. Minoda T. Kawamoto T. Akisue H. Hara Y. Onishi M. Toda R. Harada M. Morishita T. Ueha

Summary Statement

Survivin is a member of the inhibitor of apoptosis family, which may contribute to the progression of human MFH via inhibiting the mitochondrial apoptosis, and may be considered as a potent therapeutic target for the treatment of human MFH.

Introduction

Survivin is a member of the inhibitor of apoptosis (IAP) family, which usually expresses in the embryonic lung and fetal organs in the developmental stages, but is undetectable in normal adult tissues other than thymus, placenta, CD34+ stem cells, and basal colonic epitherial cells. However, several studies reported that survivin is highly expressed in various human malignancies, including sarcomas, and increased expression of survivin is an unfavorable prognostic marker correlating with decreased overall survival in cancer patients. We have previously reported that survivin was strongly expressed in human malignant fibrous histiocyoma (MFH), however, the roles of survivin in human MFH have not been studied. The aim of this study was to evaluate the effect of survivin inhibition on apoptotic activity in human MFH cells.


Y. Onishi T. Kawamoto T. Ueha H. Hara M. Toda R. Harada M. Minoda M. Morishita M. Kurosaka T. Akisue

Summary Statement

A novel transcutaneous CO2 therapy significantly enhanced the antitumor effectiveness of X-ray irradiation in human MFH xenografts The results strongly suggest that transcutaneous CO2 therapy could be a novel therapeutic tool for overcoming radioresistance in human malignancies.

Introduction

Hypoxia contributes to tumor radioresistance. In the presence of oxygen, reactive oxygen species (ROS) play crucial roles in cellular apoptosis to irradiation. We previously showed that a novel transcutaneous application of CO2 can improve hypoxia and that it induces apoptosis and decreases the expression of HIF-1α in sarcoma. Therefore, we hypothesised that a transcutaneous application of CO2 may increase radiosensitivity in sarcoma by improvement of hypoxic condition and increasing ROS production in tumors. The purpose of this study is to examine the effect of transcutaneous application of CO2 on radiosensitivity in human malignant fibrous histiocytoma (MFH) cells.


K. Trieb

Summary Statement

RANK is expressed in 18% of human osteosarcomas and is likely to provide additional prognostic information for clinical purposes in osteosarcoma patients at the time of diagnosis.

Introduction

The receptor activator of nuclear factor kappa (RANK), a member of the tumor necrosis factor family, is activated by its ligand and regulates the differentiation of osteoclasts and dendritic cells. Local growth of osteosarcoma involves destruction of the host bone by osteoclasts and proteolytic mechanisms. Although prognosis of osteosarcoma has been improved by chemotherapy during the last decades, the problem of non responders and the lack of prognostic markers remains. It is the aim of this study to investigate the prognostic and predictive value of RANK expression in human osteosarcoma.


Y. Yu N. Ibrahim J-L. Yang W. R. Walsh

Summary Statement

Combination of sorafenib with irradiation achieved synergistic effect with dose reduction in both 143B and HOS cell lines. This demonstrated the potential application of sorafenib in the treatment of osteosarcoma metastasis and radiation resistance.

Introduction

More than 20% of patients with osteosarcoma die of the disease within 5 years due to tumour relapse and metastasis. Identifying new treatment that works singly or in combination with conventional therapies is urgently required. We previously found that the Ras/Raf/MAPK pathway was associated with lung metastasis in a 143B inoculated osteosarcoma orthotopic mouse model1. Sorafenib, a multi-kinase inhibitor, has shown potent anticancer effect including in osteosarcoma2 through the inhibition of Raf-1 and other targets3. The aims of this study were to investigate effect of sorafenib on osteosarcoma cell lines with or without activated Ras/Raf/MAPK signalling and to decide whether sorafenib could enhance irradiation on these cells.


T. Tsukanishi T. Funayama M. Yamazaki S. Onishi E. Ozeki I. Hara M. Sakane

Summary

Photodynamic therapy with ICG lactosome and near-infrared light has phototoxic effects on human breast cancer cells. With the same total energy, phototoxic effects depend on output of irradiation light rather than irradiation time.

Introduction

The phototoxic effects of indocyanine green (ICG) and near-infrared light have been studied in various fields. Plasma proteins bind strongly to ICG, which is followed by rapid clearance by the liver, resulting in no tumor selectivity after systemic administration. We have proposed a novel nanocarrier labeled with ICG (ICG lactosome) that has tumor selectivity due to its enhanced permeation and retention (EPR) effect. The aim of this study was to investigate in vitro phototoxic effects and to optimise the irradiation conditions by changing the output and time of near-infrared light as excitation light.


R. Laurent L. Nicod P. Layrolle B. de Billy L. Obert F. Gindraux

Summary

Human amniotic membrane has interesting properties for regenerative medicine. To use it as an Advanced Therapeutic Medicinal Product in bone surgery, we are evaluating: the necessity of its osteodifferentiation and the impact on immunogenicity; its optimal condition for storage.

Introduction

The human Amniotic Membrane (hAM) is known to have a good potential to help the regeneration of tissues. It has been used for 100 years in many medical disciplines because of its properties: a flexible scaffold containing stem cells and growth factors, with low immunogenicity and anti-microbial, anti-inflammatory, anti-fibrotic and analgesic properties. Previous published data showed the possibility of in vitro osteodifferentiation of the whole tissue. We aim to use this «boosted membrane» as an Advanced Therapeutic Medicinal Product for bone repair to treat large defects or pseudarthrosis, so, we are studying:

The necessity to osteodifferentiate the tissue and its consequence on the immunogenicity; Its in vivo osteogenic potential; The effects of the cryopreservation on cell viability and function.


R. Laurent M. Brennan A. Renaud C. D'arros L. Obert P. Layrolle F. Gindraux

Summary

Properties of human amniotic membrane are particularly interesting. To use it as an Advanced Therapeutic Medicinal Product in bone surgery, we are evaluating its association with a potentially osteoinductive scaffold.

Introduction

The human Amniotic Membrane (hAM) is known to have a good potential to help the regeneration of tissues. It has been used for 100 years in many medical disciplines because of its properties: a membrane containing stem cells and growth factors, with low immunogenicity and anti-microbial, anti-inflammatory, anti-fibrotic and analgesic properties. Moreover, previous published data showed the possibility of in vitro osteodifferenciation of the whole tissue.

We aim to use hAM as an Advanced Therapeutic Medicinal Product for bone repair to treat large defects or pseudarthrosis. So we are studying the association of hAM with nanofiber jet sprayed polycaprolactone (PCL) scaffolds and the possibility to induce its osteodifferenciation.


V. Viateau M. Manassero H. Petite D. Logeart-Avramoglou M. Sladkova K. Oudina M. Bensidhoum

Short Summary

The present study demonstrated the feasibility of culturing a large number of standardised granular MSC-containing constructs in a packed bed/column bioreactor that can produce sheep MSC-containing constructs to repair critical-size bone defects in sheep model.

Introduction

Endogenous tissue regeneration mechanisms do not suffice to repair large segmental long-bone defects. Although autologous bone graft remains the gold standard for bone repair, the pertinent surgical technique is limited. Tissue constructs composed of MSCs seeded onto biocompatible scaffolds have been proposed for repairing bone defects and have been established in clinically-relevant animal models. Producing tissue constructs for healing bone defects of clinically-relevant volume requires a large number of cells to heal an approximately 3 cm segmental bone defect. For this reason, a major challenge is to expand cells from a bone marrow aspirate to a much larger, and sufficient, number of MSCs. In this respect, bioreactor systems which provide a reproducible and well-controlled three-dimensional (3D) environment suitable for either production of multiple or large size tissue constructs are attractive approaches to expand MSCs and obtain MSC-containing constructs of clinical grade. In these bioreactor systems, MSCs loaded onto scaffolds are exposed to fluid flow, a condition that provides both enhanced access to oxygen and nutrients as well as fluid-flow-driven mechanical stimulation to cells. The present study was to evaluate bioreactor containing autologous MSCs loaded on coral scaffolds to repair critical-size bone defects in sheep model.


A. Buizer S. Bulstra A. Veldhuizen R. Kuijer

Summary

Within hours after exposure to hypoxic circumstances hMSCs start producing AGFs. Initially hypoxia does not affect hMSC proliferation and metabolic activity, but after 7 days both are decreased, compared to hMSCs cultured under ambient oxygen conditions.

Introduction

At the moment of implantation of a large cell seeded scaffold, usually a vascular network is lacking within the scaffold. Therefore, the cells seeded on the scaffold are exposed to hypoxic circumstances. Human mesenchymal stem cells (hMSCs) exposed to hypoxic circumstances, start to produce angiogenic factors (AGF)1 and to proliferate faster than at ambient oxygen levels2. Under severe, continued hypoxia, hMSC metabolism slows down and ultimately stops3. We hypothesise that there is a threshold oxygen level above which hMSCs at hypoxia will both produce AGF and still proliferate, and below which cells slow down their metabolism. If hMSCs are provided with oxygen levels just above this threshold, effective tissue regeneration, which requires cell proliferation and vascular ingrowth, may be accomplished.


H. Chang M.J. Song M.L. Knothe Tate

Summary Statement

Flow chambers have been implemented in stem cell research to apply controlled dilational (volume changing) and deviatoric (shape changing) mechanical cues to living cells. Studies implementing such chambers demonstrate that controlled delivery of mechanical cues correlates strongly to changes in stem cell shape, structure, and fate.

Introduction

A custom designed flow chamber, capable of delivering highly controlled stresses at the cellular scale, enables the study of flow-induced normal and shear stresses on cell behavior. Specifically, computational fluid dynamics (CFD) and multiphysics modeling (coupling of CFD with finite element models) allow for controlled delivery of mechanical cues via fluid flow and cell seeding protocols, concomitant to optical mapping of cell displacements due to mechanical load, and calculation of flow velocities, imbued stresses, and cellular strains within a given volume of interest. Akin to conducting a mechanical loading test on single cells and groups of cells, paired experimental and computational experiments using the custom-designed chamber enabled calculation of the flow field's effect on the cell(s) as well as the cells’ effect on the flow field, a critical step in predicting the local stress and strain fields at the cell-fluid interface within the chamber, during exposure to fluid flow. These stresses-strains experienced by stem cells demonstrate significant correlation to cell gene expression, and strongly suggest that stresses at the cell-fluid interface influence cell fate. The current study uses a parametric approach to define next steps to prospectively guide mechanically-modulated lineage commitment.


M. Deschepper J. Paquet H. Petite

Introduction

The use of mesenchymal stem cells in regenerative medicine remains a promising approach due to the ability of these cells to differentiate into a variety of cell types of mesodermal lineage. Today, however, it is not clear whether long-term differentiation of MSCs is necessary or alternatively whether the benefits of MSCs can be conferred by transitory paracrine effects (via secreted chemical compounds). Human MSCs secrete a broad variety of cytokines, chemokines and growth factors that may potentially be involved in tissue repair. Nevertheless, hMSCs secretome profile is closely related to cells biological and chemical environment (pO2, inflammation, nutrients disponibility…). In the context of stem-cell-based regenerative medicine, upon implantation, hMSC are exposed to stresses such as ischemia, oxidative stress and inflammatory mediators. Knowledge of the paracrine properties of stem cells under hypoxic conditions is essential for planning appropriate strategies that overcome the potential negative impacts of all levels of low oxygen content (from hypoxiato anoxia) leading to ischemia and tissue necrosis pertinent to MSC-based tissue engineered constructs. Since the beneficial effects of stem cells may be confered predominantly indirectly through paracrine mechanisms, the present study was designed to characterise the hMSC secretome and to assess its biological effects considering oxygen level and nutrients disponibility.

Methods

hMSCs were exposed in vitro either to sustain ischemic environment (pO2 ≤ 0.1%, serum deprived), to hypoxia (pO2 ≤ 0.1%, 5g/L glucose) or to normoxic conditions (pO2=21%). We used an hypoxic station (Biospherix, US) to ensure sustained hypoxia during 21 days. Levels of angiogenic, chemo-attractant, inflammatory and immunomodulative mediators were assessed in supernatants using the luminex technology (milliplex KIT, Millipore, USA). The chemo-attractant potential of conditioned media (CM) was assessed in vitro using Boyden chambers (BD, USA). To assess angiogenic potential of CM, HEPC were seeded on matrigel for 18 hours with CM obtained from hMSCs. Functionnality of secreted mediators was also assessed in vivo: briefly, CM media were lyophilyzed on collagen sponges and ectopically implanted in nude mice. Chemo-attraction and vascularization of the implants were determined using histological and CTscan analysis.


D. Logeart-Avramoglou L. Monfoulet P. Becquart E. Pacard K. Vandame M. Bourguignon D. Marchat H. Petite

Summary

45S5 bioactive glass combined with hMSC did not permit de novo ectopic bone formation. Such absence of osteogenicity was most likely due to the alkalinization of the 45S5 microenvironment that affects adversely the osteogenic differentiation of stem/precursor cells.

Bone marrow stromal cells (BMSCs) are capable of bone formation and can promote the repair of osseous defects when implanted in appropriate scaffolds. The most promising biomaterials for application in bone tissue engineering (TE) are hydroxyapatite (HA), tricalcium phosphate (TCP), calcium carbonate (coral) ceramics or bioactive glasses (BG) because of their osteoconductive properties and ability to enhance bone formation. However, information regarding the osteogenic potential of hBMSCs in combination with BG scaffolds is strikingly lacking in the TE field. The present study focused on evaluating the osteogenicity of bone constructs prepared from particles of 45S5 BG combined with hBMSCs in comparison with biphasic HA/TCP or coral particles, in a mouse ectopic model.

The in vivo osteogenicity was then correlated with various aspects of the effects of the scaffold materials tested on hBMSCs functions pertinent to bone tissue formation. Particular attention was given to the pH in the microenvironment where the cells reside in TE constructs and its effect on the osteoblastic differentiation of hBMSCs. In vivo experiments evidenced that 45S5 BG constructs with hBMSCs failed to form ectopic bone. In contrast, the cell constructs prepared with either HA/TCP or coral ceramics displayed great and consistent capacity for the ectopic bone formation. The cytocompatibility of hBMSCs on BG material was addressed and no differences were evidenced between HA/TCP and coral substrates related to the adhesion of hBMSCs and their proliferation in vitro. The hBMSCs viability was even higher within the 45S5 BG-containing constructs compared to the other two types of material constructs tested both in vitro and in vivo. These findings indicated that the absence of de novo bone formation in the hBMSCs-containing 45S5 BG constructs was not the result of cytotoxic effects of the BG material.

The potential of osteogenic differentiation of hBMSCs cultured on material substrates was next addressed and the ALP activity of hBMSCs was significantly diminished when these cells were cultured on 45S5 BG as compared to either HA/TCP or coral substrates. Because BG materials are well-known for causing external alkalinisation, the pH was specifically measured in TE constructs. The pH inside the cell-containing BG constructs, measured ex vivo, was 8.0 (i.e. 0.4–0.5 units more alkaline than that measured in the coral- or HA/TCP-constructs). The impact of such external alkalinisation on the osteogenic differentiation of hBMSCs was assessed by culturing the cells over a wide range of alkaline pH. The hBMSCs expression of osteogenic markers, ALP activity and mineralization were not significantly affected at moderate external alkaline pH (≤ 7.90) but were dramatically inhibited at higher pH.

Altogether, these findings provided evidence that despite 45S5 BG are reported to be good osteoconductive materials, they are not necessarily good scaffolds for TE, most likely due to the alkalinization of the 45S5 microenvironment that affects adversely the osteogenic differentiation of precursor cells. Controlling the shifts of pH in the local engineered extracellular environment is a critical issue for the development of bioactive TE scaffolds.


A. Razak A. Ebinesan C.P. Charalambous

Summary Statement

Routine metal allergy screening prior to joint arthroplasty is not essential and the use of cobalt chromium or stainless steel implants is recommended regardless of the patient's metal allergy status.

Introduction

This study was undertaken to obtain a consensus amongst joint arthroplasty experts with regards to metal allergy screening prior to joint arthroplasty and the choice of implant in patients with potential metal allergy.


E.-Y. Chan F.M. Blyth L. Nairn M. Fransen

Summary Statement

There were significant differences in the pain experience, behaviors, and perceptions on analgesics, between the Australia and Singapore cohorts, after hospital discharge following TKR. These findings may be influenced by the ethnicity and cultural differences between these two countries.

Introduction

In recent years the hospital length of stay after total knee replacement (TKR) has shortened. Hence, patients have to self-manage their pain earlier after the surgery. The aim of this study was to examine if the pain experience, self-management behaviors and potential barriers to optimal analgesia after hospital discharge for TKR differed in different ethnicity groups.


B. Boonen M. Schotanus B. Kerens W.r van der Wegen N. Kort

Summary

Alignment results did not differ between PSG and conventional instrumentation. A small reduction in operation time and blood loss was found with the PSG system, but is unlikely of clinical significance. Length of hospital stay was identical for both groups.

Introduction

Several techniques for aligning a TKA exist nowadays. Patient-specific guiding (PSG) has relatively recently been introduced to try to resolve the shortcomings of existing techniques while optimising the operative procedure. Still few reports have been published on the clinical outcome and on the peroperative results of this new technique. This prospective, double-blind, randomised controlled trial was designed to address the following research questions: 1. Is there a significant difference in outliers in alignment in the frontal and sagittal plane between PSG TKA and conventional TKA. 2. Is there a significant difference in operation time, blood loss and length of hospital stay between the 2 techniques.


V. Moretti A. Gordon

Summary Statement

Navigated total knee arthroplasty (TKA) is becoming increasingly popular in the United States. Compared to traditional unnavigated TKA, the use of navigation is associated with decreased blood transfusions and shorter hospital stays.

Introduction

Navigated total knee arthroplasty (TKA) is a recent modification to standard TKA with many purported benefits in regards to component positioning. Controversy currently exists though regarding its clinical benefits. The purpose of this study was to assess recent national trends in navigated and unnavigated total knee arthroplasty and to evaluate perioperative outcomes for each group.


B. Kerens B. Boonen M. Schotanus N. Kort

Summary Statement

This is the first report of a new technique for unicompartmental to total knee arthroplasty revision surgery in which patient specific guides are formed based on preoperative CT imaging. This technique can help to make revision surgery less technically demanding.

Introduction

Unicompartmental to total knee arthroplasty revision surgery can be a technically demanding procedure. Joint line restoration, rotation and augmentations can cause difficulties. This study describes a new technique in which single way fitting guides serve to position knee system cutting blocks.


R. Papalia G. Vadala F. Franceschi L. Diaz Balzani B. Zampogna S. D'Adamio N. Maffulli V. Denaro

Introduction

Ostochondral lesion of the knee is a common cause of chronic knee pain. Arthroscopic treatment with subcondral microfracture is a widespread technique leading to noticeable improvement of knee function and pain. To improve the effectiveness of this treatment options, we thought to add intra (PRF) or post-operative (PRP) growth factors. Platelet rich plasma (PRP) is obtained by centrifugation of the blood to produce a plasma with high concentration of platelets and growth factors. This latter represents a promising method to manage degenerative cartilage lesion and can be used postoperatively to improve clinical results of patients treated arthroscopically. Platelet Rich Fibrin (PRF) has been presented as a second-generation platelet concentrate, and it is used intraoperatively to cover the microfracuteres’ holes. No literature was found about using of PRF intraoperative in association with arthroscopic microfracture technique. The aim of this study is to compare clinical outcomes of the treatment of knee osteochondral lesion using arthroscopic microfracture technique alone or in association with PRF Intraoperative application using “Vivostat” system or with PRP “ReGen Lab” postoperative injection.

Patients & Methods

90 patients with clinical and radiographic evidence of osteochondral lesion of the medial or lateral compartment of the knee were enrolled. All patients received arthroscopic debridement and Microfractures and were randomised into 3 groups: 30 patients received microfractures and intraoperative PRF “Vivostat” injection(Group A), 30 patients received microfracture and 3 intra-articular injections of 5.5 mL PRP “Regen”(Group B), 30 patients received microfracture only. IKDC, KOOS and VAS score were administered to all patients before starting the treatment, at 1, 6 and 12 months from the end of the management.


A. Boissonneault J. Lynch B. Wise N. Segal D. Gross M. Nevitt D. Murray H. Pandit

Summary

Anatomical variations in hip joint anatomy are associated with both the presence and location of tibiofemoral osteoarthritis (OA).

Introduction

Variations in hip joint anatomy can alter the moment-generating capacity of the hip abductor muscles, possibly leading to changes in the magnitude and direction of ground reaction force and altered loading at the knee. Through analysis of full-limb anteroposterior radiographs, this study explored the hypothesis that knees with lateral and medial knee OA demonstrate hip geometry that differs from that of control knees without OA.


A. Eguchi M. Ochi N. Adachi M. Deie A. Nakamae T. Nakasa

Summary Statement

We evaluated the mechanical strength of two cortical suspension devices by reproducing clinical situation for ACL reconstruction. A most important factor affecting the displacement during cyclic load was the length of the tendon rather than the length of the device.

Introduction

A definite consensus for the optimal graft fixation technique to the femur in an anterior cruciate ligament (ACL) reconstruction has not been reached, although there have been several fixation techniques such as cortical suspension devices, transfixation devices, and interference screws. The purpose of this study was to evaluate the mechanical strength of two cortical suspension devices by reproducing actual clinical situation for ACL reconstruction in order to compare the TightRopeTM as a new adjustable-length loop device and the EndoButtonTM as a well-known fixed-length loop device under the consistent conditions.


J. Boyd H. Gill A. Zavatsky

Summary Statement

Simulated increases in body weight led to increased displacement, von Mises stress, and contact pressure in finite element models of the extended and flexed knee. Contact shifted to locations of typical medial osteoarthritis lesions in the extended knee models.

Introduction

Obesity is commonly associated with increased risk of osteoarthritis (OA). The effects of increases in body weight and other loads on the stresses and strains within a joint can be calculated using finite element (FE) models. The specific effects for different individuals can be calculated using subject-specific FE models which take individual geometry and forces into account. Model results can then be used to propose mechanisms by which damage within the joint may initiate.


J. Mellema J. Doornberg T. Quitton D. Ring

Summary

Biomechanical studies comparing fixation constructs are predictable and do not relate to the significant clinical problems. We believe there is a need for more careful use of resources in the lab and better collaboration with surgeons to enhance clinical relevance.

Introduction

It is our impression that many biomechanical studies invest substantial resources studying the obvious: that open reduction and internal fixation with more and larger metal is stronger. Studies that investigate “which construct is the strongest?” are distracted from the more clinically important question of “how strong is strong enough?”. The aim of this study is to show that specific biomechanical questions do not require formal testing. This study tested our hypothesis that the outcome of a subset of peer reviewed biomechanical studies comparing fracture fixation constructs can be predicted based on common sense with great accuracy and good interobserver reliability.


P. Oomen K. Meijer R.G. van der Westen R. Gransier P. Emans L. van Rhijn

Summary

The quantification of T1Rho relaxation times is not related with internal loading. Improvements in modeling and imaging techniques might lead to better understanding of the pathomechanics of the knee.

Introduction

The onset and progression of knee osteoarthritis has been associated with an increased external knee adduction moment (EKAM). However, this external measure has no direct relationship with internal loading of the knee. For a better understanding of the pathomechanics of the knee musculoskeletal models could be used to relate external and internal knee loading. Consequently, high internal loading might cause cartilage degeneration in patients with OA. T1RhoMRI can detect changes in proteoglycan content and is therefore a non-invasive measure of cartilage degeneration in knee OA. The purpose of this study was to relate internal loading of the knee simulated by musculoskeletal models with cartilage health using T1rhoMRI.


K. Schneider I. Zderic B. Gueorguiev R.G. Richards S.E. Nork

Summary

Biomechanically, a 2° screw deviation from the nominal axis in the PFLCP leads to significantly earlier implant failure. Screw deviation relies on a technical error on insertion, but in our opinion cannot be controlled intraoperatively with the existing instrumentation devices.

Background

Several cases of clinical failure have been reported for the Proximal Femoral Locking Compression Plate (PFLCP). The current study was designed to investigate the failure mode and to explore biomechanically the underlying mechanism. Specifically, the study sought to determine if the observed failure was due to technical error on insertion or due to implant design.


A. van der Veen A. Bisschop M. Mullender J. van Dieen

Summary Statement

Creep behaviour can only be quantified accurately when the testing time exceeds the estimated time constant of the creep process. The new parameters obtained in this paper can be used to describe normal behaviour up to 24 hrs.

Background

Diurnal loading on the human spine consists of 16hrs loading and 8hrs rest. After an initial load increase, due to rising in the morning, an axial loading is maintained throughout the day. As a consequence subsidence of the intervertebral disc (IVD) occurs during the day while disc height recovers during the night. This behaviour is time dependent (non-linear). In literature different constitutive equations have been used to describe creep. A stretched exponential (Kolraush-Wilson-Watts, KWW) and a double Voight (DV) model have both been used to quantify the creep behaviour. Using these models, time constants and the deformation at equilibrium are estimated. It is unsure whether these different approaches yield to valid predictions. In this study we compared the validity of different equations for the prediction of creep behavior.


E. Bonnevie D. Galesso C. Secchieri L. Bonassar

Summary

Both endogenous lubricin and injectable hyaluronic acid reduced cartilage friction coefficients, but by distinct mechanisms. Lubricin operated in boundary mode and hyaluronic acid shifted lubrication to mixed or hydrodynamic mode.

Introduction

Intra-articular injections of viscous agents and boundary lubricants have been presented as options to mitigate the progression of articular cartilage damage after the onset of osteoarthritis1,2. Mechanically, these injections are predicted to lower the friction coefficient within a load bearing joint and consequently slow the propagation of damage at the articular surface. Tribologically, boundary lubricants and viscous agents are hypothesised to be effective through different mechanisms affecting boundary-mode lubrication and transition to mixed-mode lubrication, respectively. By normalizing sliding speeds on a Stribeck curve, this study evaluated the efficacy of injectable hyaluronic acid (HA) supplements and endogenous lubricin to alter tribological properties.


C. O'Kane A. Vrancken D. O'Rourke D. Janssen M. Ploegmakers P. Buma D. Fitzpatrick N. Verdonschot

Summary

Our statistical shape analysis showed that size is the primary geometrical variation factor in the medial meniscus. Shape variations are primarily focused in the posterior horn, suggesting that these variations could influence cartilage contact pressures.

Introduction

Variations in meniscal geometry are known to influence stresses and strains inside the meniscus and the articulating cartilage surfaces. This geometry-dependent functioning emphasizes that understanding the natural variation in meniscus geometry is essential for a correct selection of allograft menisci and even more crucial for the definition of different sizes for synthetic meniscal implants. Moreover, the design of such implants requires a description of 3D meniscus geometry. Therefore, the aim of this study was to quantify 3D meniscus geometry and to determine whether variation in medial meniscus geometry is size or shape driven.


Y. Cai J. Li H.C. Tan E.S. Thian J.Y. Hsi Fuh B.Y. Tay W. Wang

Summary Statement

A three dimensional meniscal scaffold with controlled fibre diameter and orientation was fabricated by an improved E-Jetting system that mimic the internal structure of natural meniscus. In vitro cellular tests proved its feasibility in meniscal tissue engineering applications.

Introduction

Current surgical and repair methods for complex meniscal injuries still do not often give satisfactory long-term results. Thus, scaffold-based grafts are the subject of much research interest. However, one major hurdle is that current techniques are unable to replicate the precise 3D microstructure of meniscus, nor the variations in the fibrillar structure and tissue content from layer to layer. In this work, an improved electrohydrodynamic jet printing system (E-Jetting system) was developed to fabricate biomimetic meniscal scaffold for tissue regeneration.


C. Brochhausen D. Grevenstein J. Grevenstein A. Mamilos V.H. Schmitt C.J. Kirkpatrick

Summary Statement

Re-biopsies of five patients after spheroid-based, scaffold-free autologous chondrocyte transplantation revealed regeneration of cartilage with immunohistochemical characteristics of articular cartilage.

Introduction

Traumatic lesions of articular cartilage represent a crucial risk-factor for cartilage degradation and osteoarthritis, because the regenerative capacity of articular cartilage is highly limited. Even if there exist several strategies to treat traumatic cartilage damages such as the classical autologous chondrocyte transplantation (ACT) or matrix assisted ACT, the optimal solution is not yet been found since transplantation errors are known. A relatively new strategy represents the scaffold-free spheroid based autologous chondrocyte transplantation. After harvesting articular cartilage in this strategy spheroids of chondrocytes will be synthesised after chondrocyte isolation and expansion. The spheroids will be implanted and rest at the transplantation site by adhesion.


J. Penny M. Ding O. Ovesen J.E. Varmarken S. Overgaard

Summary

Despite high revision rates, the mean two year migration of the ASRTM cup is within an acceptable threshold. Slightly higher migration rates found for the M2a- Magnum™ Porous Coated Acetabular Component but longer follow up is needed to establish if this implant is at risk.

Introduction

RSA can detect the migration of an implant, and continuous migration is a predictor for failure (1). The ASRTM resurfacing implant was withdrawn from the marked due to excessive failure rate but showed initial femoral component stability. The aim of this study was to investigate the initial implant stability for the ASR cup as a possible explanation for the high revision rate, and to compare it to another metal on metal (MoM) cup.


B. Shareghi J. Kärrholm

Summary

Comparison of accuracy and precision in measuring wear using 4 commonly used uncemented cup designs shows small differences in mean and data scatter for marker and model-based RSA.

Introduction

The disadvantage with conventional RSA is that implant has to be supplied with tantalum markers, which may be difficult to visualise. This problem can be resolved with model-based RSA, but it is uncertain if this method has the same precision as marker-based RSA to measure wear. We compared these methods and studied different prosthesis geometries represented by four different uncemented cup designs (Trilogy, TMT-Trabecular Metal, Zimmer, Warsaw, USA, Ringloc, Biomet, Inc., Warsaw, Indiana, and ABG, Howmedica International, Staines, UK).


E. Verboom E. van Ijsseldijk E. Valstar B. Kaptein R. de Ridder

Summary

In this study we validate that weight-bearing images are needed for accurate polyethylene liner wear measurement in total knee prostheses by measuring the difference in minimum joint space width between weight-bearing and non-weight-bearing RSA views.

Introduction

Recent studies show that Model-based Roentgen Stereophotogrammetric Analysis is superior to the conventional in vivo measurements of polyethylene liner wear in total knee prostheses. Although it is generally postulated that weight-bearing (standing) views are required to detect liner wear, most RSA images are acquired in non-weight-bearing (supine) view for practical reasons. Therefore, it would be of interest to know if supine views would be sufficient for measuring TKA liner wear, defined as a change in minimum joint space width (mJSW). As a difference in mJSW between weight-bearing and non-weight-bearing RSA images has never been validated, the aim of this study is to compare the outcome of in vivo measurements of mJSW in total knee prosthesis when conducted with weight-bearing and non-weight-bearing RSA views.


D. Ayers B. Snyder A. Porter M. Walcott M. Aubin J. Drew M. Greene C. Bragdon

Summary Statement

In young, active patients cementless THR demonstrates excellent prosthetic stability by RSA and outstanding clinical outcomes at 5 years using a tapered titanium femoral stem, crosslinked polyethylene liners and either titanium or tantalum shells.

Introduction

Early femoral implant stability is essential to long-term success in total hip replacement. Radiostereometric analysis (RSA) provides precise measurements of micromotion of the stem relative to the femur that are otherwise not detectable by routine radiographs. This study characterised micromotion of a tapered, cementless femoral stem and tantalum porous-coated vs. titanium acetabular shells in combination with highly cross-linked UHMWPE or conventional polyethylene liners using radiostereometric analysis (RSA) for 5 years following THR.


M. Hjorth K. Søballe S. Jakobsen N. Lorenzen I. Mechlenburg M. Stilling

Summary

Five year migration results of 49 large-head metal-metal (MoM) total hip arthroplasties show good implant stability and no association between implant migration and metal-ions levels, stem and cup position, or femoral bone mineral density.

Introduction

The failure mechanism of metal-metal (MoM) total hip arthroplasty has been related to metal wear-debris and pseudotumor, but it is unknown whether implant fixation is affected by metal wear-debris.


M. Meijer A. Boerboom M. Stevens S. Bulstra I. Reininga

Summary

The EOS stereography system has been developed for the evaluation of prosthetic alignment. This new low-dose device provides reliable 2D/3D measurements of knee prosthesis alignment.

Introduction

Achieving optimal prosthetic alignment during Total Knee Arthroplasty (TKA) is an essential part of the surgical procedure since malpositioning can lead to early loosening of the prosthesis and eventually revision surgery. Conventional weight-bearing radiographs are part of the usual clinical follow-up after both primary TKA and revision TKA (rTKA), to assess alignment in the coronal and sagittal planes. However, proportions and angles may not be correct on radiographs since divergence exists in the vertical and horizontal planes. Furthermore estimating the exact planes by looking at the position of the patella depends on rotation in the hip joint and this may be misinterpreted by the investigator. A computed tomography (CT) scanogram can also be used. However, due to high levels of radiation and costs it is not routinely used. To this end, a new device, the EOS stereography system, has been developed. With this biplanar low-dose X-ray technique, orthogonally made 2D images and 3D reconstructions can be obtained. Advantages of EOS are that images of the leg are obtained on a 1:1 scale with an amount of radiation 800–1000 times lower than CT-scans and 10 times lower than conventional radiographs. Another advantage is that the 3D reconstructions lead to determination of the real coronal and sagittal planes. However, the software for creating 3D reconstructions is developed for the lower limbs without knee prosthesis material. Consequently a reliability study concerning the generation of 2D images and 3D reconstructions of a leg containing a knee prosthesis has not been performed yet. Therefore objective of this study was to investigate interobserver and intraobserver reliability of knee prosthetic alignment measurements after rTKA using EOS.


M. Mohaddes H. Malchau P. Herberts P.-E. Johansson J. Kärrholm

Summary Statement

We analysed impaction bone grafting used together with cemented or uncemented fixation in acetabular revision surgery. The overall risk for re-revision did not differ between the cemented and uncemented group. However, aseptic loosening was more common in the cemented group.

Background

Several surgical techniques address bone defects in cup revision surgery. Bone impaction grafting, introduced more than thirty years ago, is a biologically and mechanically appealing method. The primary aim of this study was to evaluate the effect of bone impaction grafting when used with uncemented and cemented fixation in cup revision surgery. Uncemented cups resting on more than 50% host bone were used as controls.


D. Schroeder S. Durham M. Elliott

Summary Statement

A new 28mm-diameter ceramic-on-ceramic (COC) acetabular bearing couple (Biomet Orthopedics) showed extremely low wear, even under adverse microseparation conditions∗. The wear results are similar or more favorable than those reported for clinical retrievals and wear testing of similar ceramic bearings.

Introduction

A new acetabular shell and ceramic insert design (Biomet) incorporates features to help prevent malalignment during implantation, while still providing secure fixation within the acetabular shell. The incorporation of Biolox® Delta (zirconia toughened alumina, CeramTec) material should provide improved wear resistance over pure alumina ceramics. The goal of this study is to evaluate the wear durability of this system for standard and microseparation testing.


M. Al-Hajjar J. Fisher C. Hardaker G. Kurring G. Isaac S. Williams

Summary Statement

The frictional torque of ceramic-on-ceramic bearings tended to increase with increasing the bearings size (32, 48, 56mm). However, the frictional torque was significantly lower than that measured on metal-on-metal bearings under well positioned and well lubricated conditions.

Introduction

Larger head size in total hip replacement theoretically provides increased range of motion and enhanced stability. However, there are potential clinical concerns regarding increased frictional torques with large diameter metal-on-metal bearings causing loosening of the acetabular cups and corrosion at the taper. The aim of this study was to determine the frictional torques of large diameter BIOLOX® delta ceramic-on-ceramic bearings.


S. Kurtz D. MacDonald G. Higgs J. Gilbert G. Klein M. Mont J. Parvizi M. Kraay C. Rimnac

Summary Statement

Fretting and corrosion has been identified as a clinical problem in modular metal-on-metal THA, but remains poorly understood in modern THA devices with polyethylene bearings. This study investigates taper damage and if this damage is associated with polyethylene wear.

Introduction

Degradation of modular head-neck tapers was raised as a concern in the 1990s (Gilbert 1993). The incidence of fretting and corrosion among modern, metal-on-polyethylene and ceramic-on-polyethylene THA systems with 36+ mm femoral heads remains poorly understood. Additionally, it is unknown whether metal debris from modular tapers could increase wear rates of highly crosslinked PE (HXLPE) liners. The purpose of this study was to characterise the severity of fretting and corrosion at head-neck modular interfaces in retrieved conventional and HXLPE THA systems and its effect on penetration rates.


U. Wyss R. Dyrkacz O. Ojo T. Turgeon J. Brandt

Summary

Corrosion and fretting damage at the head-neck interface of artificial hip joints is more severe with larger head sizes. This is a concern, as the release of metal particles and ions can cause adverse tissue reactions, similar to those observed high wear metal-on-metal articulations.

Introduction

In the last few years corrosion was increasingly observed at head-neck interfaces of artificial hip joints, especially in joints with larger heads. There has always been evidence of some corrosion at modular junctions of artificial joints, but except for few designs, it was not seen as a real problem. It is important to better understand the factors contributing to corrosion at modular interfaces, so that necessary improvements can be made to minimise or completely avoid corrosion, in order to avoid possible adverse tissue reactions.


N. Dong J. Nevelos S. Kreuzer

Summary

From a large 3D Caucasian bone data base, female population had significantly larger acetabular anatomical anteversion angle and combined acetabular-femoral anteversion angle than that of male population. There was no significant difference in femoral neck anteversion angles between the groups.

Introduction

Combined Anteversion (CA) angle of acetabular component and femoral neck is an important parameter for a successful Total Hip Arthroplasty (THA). The purpose of this study was to electronically measure the version angles of native acetabulum and femur in matured normal Caucasian population from large 3D CT data base. Our question was if there was any significant difference in CA between male and female population.


C. Smeekes B.F. Ongkiehong B.C.H. van der Wal

Summary

The M2a-38tm metal on metal total hip arthroplasty showed a high incidence of pseudotumors and an unexpected high revision rate in our thoroughly screened cross sectional cohort.

Introduction

After the revival of the metal on metal (MoM) bearing in total hip arthroplasty (THA) at the beginning of this century, there are now serious questions about this type of bearing. The advantage of large head MoM bearing is the increase in range of motion and stability. In our institution the choice was made for 38 mm heads. During the last few years concerns have been raised about the relationship of MoM bearing and elevated serum cobalt and chromium ion levels, their local and systemic toxicological effects and the incidence of local tumorous masses (pseudotumors). Are these findings applicable for all MoM bearings or are there also product specific issues. We present the outcome of a cementless MoM THA using a 38mm head in a unique consecutive series of 377 THA who were performed in our institution.


S. Slagis N. Skrepnik J. Wild M. Robertson B. Nielsen T. Skrepnik R. Eberle

Summary

Management of metal on metal hip replacements can be accomplished with a simple algorithm including easily available metal ion levels and hip MRI with metal artifact reducing software. After revision serum metal ion levels can be expected to fall rapidly.

Introduction

Metallic ion release may be related to bearing surface wear and thus serves as an indicator of the in-vivo performance of metal on metal articulations. The purpose of this prospective, controlled study was to compare new large head metal on metal hip components with established modular metal on metal and metal on polyethylene and to determine their effects on serum metal levels before and after revision.


M. Yiasemidou D. Teanby U. Munir

Summary Statement

This study assesses the service provision of viscosupplementation within an NHS (British National Health System) hospital. The results of this study show long term efficacy of the treatment, when provided by a dedicated, orthopaedic unit.

Introduction

The service provision of viscosupplementation for osteoarthritis within the National Health System (NHS) remains controversial. The treatment was recommended in the 2007 NICE guidelines but support was withdrawn the following year. Furthermore, whether it should be provided by orthopaedic surgeons or in primary care is also a matter of debate. St Helens and Knowsley Trust, runs an orthopaedic outpatient clinic dedicated to the administration of viscosupplementation to patients with symptomatic knee osteoarthritis. This study aims to assess the efficacy of viscosupplementation for knee osteoarthritis when that is provided by a highly specialised, orthopaedic, dedicated service


J. van Leeuwen S. Röhrl B. Grøgaard F. Snorrason

Summary Statement

Our data suggest that postoperative component positioning in TKA with PSPG is not consistent with pre-operative software planning. More studies are needed to rule out possible learning curve in this study.

Introduction

Patient specific positioning guides (PSPGs) in TKA are based on MRI or CT data. Preoperatively, knee component positions can be visualised in 3-dimensional reconstructed images. Software allows anticipation of component position. From software planning PSPGs are manufactured and those PSPGs represent intra-operative component alignment. To our knowledge, there are no studies comparing pre-operative software planning with post-operative alignment. Aim of this study is to investigate the correlation between pre-operative planning of component positioning and the post-operative achieved alignment with PSPG technique.


M. Simons P. Riches

Summary Statement

Uptake of robotically-assisted orthopaedic surgery may be limited by a perceived steep learning curve. We quantified the technological learning curve and 5 surgeries were found to bring operating times to appropriate levels. Implant positioning was as planned from the outset.

Introduction

Compared to total knee replacement, unicondylar knee replacement (UKR) has been found to reduce recovery time as well as increase patient satisfaction and improve range of motion. However, contradictory evidence together with revision rates concern may have limited the adoption of UKR surgery. Semi-active robotically-assisted orthopaedic tools have been developed to increase the accuracy of implant position and subsequent mechanical femorotibial angle to reduce revision rates. However, the perceived learning curve associated with such systems may cause apprehension among orthopaedic surgeons and reduce the uptake of such technology. To inform this debate, we aimed to quantify the learning curve associated with the technological aspects of the NavioPFS™ (Blue Belt Technologies Inc., Pittsburgh, USA) with regards to both operation time and implant accuracy.


L. Song L.Q. Loving W. Xia Z. Song N. Zacharias P. Wooley

Summary Statement

Antioxidant containing UHMWPE particles induced similar levels of in vitro macrophage proliferation and in vivo inflammation in the mouse air pouch model as UHMWPE particles alone. Benefit of antioxidant in reducing wear particle induced inflammation requires further investigation.

Introduction

Wear particles derived from UHMWPE implants can provoke inflammatory reaction and cause osteolysis in the bone, leading to aseptic implant loosening. Antioxidants have been incorporated into UHMWPE implants to improve their long term oxidative stability. However it is unclear if the anti-inflammatory property of the antioxidant could reduce UHMWPE particle induced inflammation. This study evaluated the effect of cyanidin and vitamin E on UHMWPE induced macrophage activation and mouse air pouch inflammation.


S. Kurtz O. Zielinska D. MacDonald H. Cates M. Mont A. Malkani J. Parvizi M. Kraay C. Rimnac G. Klein

Summary Statement

This study assesses oxidation, mechanical behavior and revision reasons of 2nd generation HXLPE used in total hip and knee arthroplasty. While oxidation was low for both X3 and E1 HXLPEs, oxidative regional variations were detected in the sequentially annealed cohort.

Introduction

First generation highly crosslinked polyethylenes (HXPLEs) have proven successful in lowering both penetration and osteolysis rates. However, 1st generation annealing and remelting thermal stabilization have been associated with in vivo oxidation or reduced mechanical properties. Thus, 2nd generation HXLPEs were developed to improve oxidative stability while still maintaining material properties. Little is known about the in vivo clinical failure modes of these 2nd generation HLXPEs. The purpose of this study was to assess the revision reasons, wear, oxidative stability, and mechanical behavior of retrieved sequentially annealed Vitamin E diffused HXLPE in THA and TKA.


R. Hutchinson Q. Choudry G. McLauchlan

Summary

The 80% porous structure of trabecular metal allows for bone ingrowth in more than 90% of the available surface. The Nexgen LPS Uncemented Knee using a trabecular metal tibial component has performed well at minimum of 5 years’ follow-up.

Introduction

Total Knee Arthroplasty prostheses most frequently used in today's practice have cemented components. These have shown excellent clinical results. The fixation can however weaken with time, and cement debris within the articulation can lead to accelerated wear. Cementless implants are less commonly used, but some have also shown good long-term clinical results. The potential advantages of cementless implants are retention of bone stock, less chance of third-body wear due to the absence of cement, shorter operative time, and easier treatment of periprosthetic fractures. The posterior stabilised knee replacement has been said to increase tangential shear stresses on the tibial component and increases contact stresses on the cam and post mechanism hence the great debate of cruciate retaining or cruciate sacrificing implants.


L.G. Fitzgerald A. Titchener A.W. Miles

Summary Statement

The tensile properties of a number of synthetic fibre constructs and porcine MCLs were experimentally determined and compared to allow the selection of an appropriate synthetic collateral ligament model for use in a kinematic knee simulator.

Introduction

As patient expectations regarding functional outcomes of total knee arthroplasty rise the need to assess the kinematics of new implants in vitro has increased. This has traditionally been done using cadaveric models, which can demonstrate high physiological relevance but also substantial inter-specimen variability. More recently there has been a shift towards the use of in silico and non-cadaveric methods. Such methods require significant simplifications of the joint and the modelling of soft tissue structures such as the collateral ligaments. Collateral ligaments are often modelled in in silico studies but have not, in the published literature, been modelled in in vitro knee kinematic simulators. Tensile testing of ligament tissue, to provide reference data, and the subsequent analysis of potential synthetic analogues was carried out. The overall aim of the study was to develop a synthetic ligament analogue for use in kinematic knee simulators.


P. Heuberer V. Lovric N. Russell J. Goldberg W. Walsh

Summary Statement

Demineralised bone matrix augmented tendon-bone fixations in the animal model show less scar tissue and an enthesis morphology closer to the physiologic one which may lead to a more resistant repair construct.

Introduction

Rotator cuff repair is one of the most common operative procedures in the shoulder. Yet despite its prevalence recurrent tear rates of up to 94% have been reported in the literature. High failure rates have been associated with tendon detachment from bone at the tendon – bone interface. Exogenous agents as biological strategies to augment tendon – bone healing in the shoulder represent a new area of focus to improve patient outcomes. Demineralised bone matrix (DBM) contains matrix bound proteins, exposed through acid demineralization step of DBM manufacture, and has long been recognised for its osteoinductive and osteoconductive properties. We hypothesised that DBM administered to the bone bed prior to the reattachment of the tendon, will upregulate healing and result in enhanced tissue morphology that more closely resembles that of a normal enthesis. An established ovine transosseous equivalent rotator cuff model was used.


S. Elnikety C. Pendegrass C. Holden G. Blunn

Summary

Our results prove that Demineralised Cortical Bone (DCB) can be used as biological tendon graft substitute, combined with correct surgical technique and the use of suture bone anchor early mobilisation can be achieved.

Introduction

Surgical repair of tendon injuries aims to restore length, mechanical strength and function. In severe injuries with loss of tendon substance a tendon graft or a substitute is usually used to restore functional length. This is usually associated with donor site morbidity, host tissue reactions and lack of remodelling of the synthetic substitutes which may result in suboptimal outcome. In this study we hypothesise that DCB present in biological tendon environment with early mobilisation and appropriate tension will result in remodelling of the DCB into ligament tissue rather that ossification of the DCB at traditional expected. Our preparatory cadaveric study (abstract submitted to CORS 2013) showed that the repair model used in this animal study has sufficient mechanical strength needed for this animal study.


S. Elnikety C. Pendegrass S. Alexander G. Blunn

Summary

Our study shows that a tendon rupture can be successfully augmented with Demineralised Cortical Bone (DCB) giving initial appropriate mechanical strength suitable for in vivo use providing the biological reactions to the graft are favourable.

Introduction

Treatment of tendon and ligament injuries remains challenging; the aim is to find a biocompatible substance with mechanical and structural properties that replicate those of normal tendon and ligament. Because of its structural and mechanical properties, we proposed that DCB can be used in repair of tendon and ligament as well as regeneration of the enthesis. DCB is porous, biocompatible and has the potential to be remodelled by the host tissues. 2 studies were designed; in the first we examined the mechanical properties of DCB after gamma irradiation (GI) and freeze drying (FD). In the second we used different techniques for repairing bone-tendon-bone with DCB in order to measure the mechanical performance of the construct.


T. Kanazawa M. Gotoh K. Ohta A. Togou R. Higashi N. Shiba K. Nakamura

Summary Statement

Tendon-bone interface becomes matured with the perforating fiber and the cells striding over the bone area. We suggest that both “perforating fiber” and “cell stride” could play a crucial role in regeneration after rotator cuff repair.

Introduction

To obtain a successful outcome after rotator cuff repair, repaired tendon requires to be anchored biologically to the bone. However, it is well known that the histological structure of the repaired tendon-bone insertion is totally different from the normal insertion. This morphological alteration may contribute to biological instability after surgical repair. To address these issues, it is fundamental to clarify the difference of the structure between the normal and the repaired insertion in detail. Surprisingly, few studies on the tendon-bone insertion using electron microscopy has been performed so far, since the insertion area is solid (bone/cartilage) and extremely limited for the analysis. Recently, a new scanning electron microscopical method (FIB/SEM tomography) has been developed, making it possible to analyze the wider area with the higher resolution and reconstruct 3D ultrastructures. The purpose of this study was to analyze the ultrastructure of the repaired supraspinatus tendon-bone insertion in rat using FIB/SEM tomography.


E. Jones K. Legerlotz G. Riley

Summary Statement

We have shown that integrin mRNA expression is regulated by the application of mechanical load. This indicates that mechanical loading may modify cell sensitivity to perceive further load through increased interaction with the ECM.

Introduction

Tendinopathies are a range of diseases characterised by pain and insidious degeneration. Although poorly understood, onset is often associated with physical activity. We have previously investigated the regulation by mechanical strain of metalloproteinase gene expression in human tenocyte in a 3D collagen matrix. Integrins are important in cellular interaction with the ECM and are reported to mediate mechanotransduction in various non-tendon tissues. We have reported that TGFbeta activation is a key player in the regulation of metalloproteinases in response to mechanical load, which may be mediated by integrins. This project aims to investigate the effect of cyclic loading and TGFbeta stimulation on integrin expression by human tenocytes, in collagen and fibrin matrices.


C. Thorpe G. Riley H. Birch P. Clegg H. Screen

Summary Statement

Fatigue loading has an age-specific effect on tendon fascicle micro-mechanics, with greater fibre sliding in aged samples indicating a decreased mechanical integrity, and a reduced ability to withstand cyclic loading, which may partially explain the age-related risk of tendon injury.

Introduction

The human Achilles and equine superficial digital flexor (SDFT) tendons function as energy stores, experiencing large, repetitive stresses and strains1 and are therefore highly susceptible to injury, particularly in aged individuals. We have previously observed rotation within SDFT fascicles in response to applied strain, which indicates the presence of helical sub-structures within this tendon. Further, we have shown that this rotation decreases with ageing, suggesting alterations to the helix sub-structure and a difference in the extension mechanisms in aged tendons. We therefore hypothesise that cyclic fatigue loading (FL) will result in alterations in fascicle extension mechanisms which are age specific.


D. Zeugolis

Summary

Tissue grafts fail to recapitulate native tendon function, imposing the need for development of functional regeneration strategies. Herein, we describe advancements in tendon repair and regeneration using functionalised natural and synthetic devices and scaffold-free cell-based therapies.

Introduction

Tendon and ligament injuries constitute an unmet clinical need with approximately 100,000 new cases annually in US alone. Tissue grafts are considered the gold standard in clinical practice. However, allografts and xenografts can lead to potential disease transmission, whilst the limited supply of autografts in severe injuries and degenerative conditions restricts their use. To this end, scaffold and scaffold-free therapies are under development to address the tissue grafts shortage. Herein, we describe biophysical, biochemical and biological methods to maintain tendon derived cell phenotype and/or differentiation of other cell types towards tenogenic lineage; development of tendon-equivalent facsimiles; and ultimately functional neotendon formation.


Y. Tochigi N. Segal

Summary

Measurement of changes in the physiological cycle-to-cycle variability in gait kinematics using the ELLIS approach holds promise as a new tool for quantitative evaluation of gait adaptability.

Introduction

Adaptability is arguably one of the most crucial factors of gait function. However, functional limitations in adaptability have not been well documented, presumably due to the inability to accurately measure this aspect. For this purpose, we developed a new method to quantify subtle changes in cycle-to-cycle physiological variability in gait kinematics; a technique designated as the entropy of leg-linkage inertial signals (ELLIS) analysis. A previous study (Tochigi et al., JOR 2012) found that the ELLIS outputs in an asymptomatic cohort) became lower with greater age, and that subjects with symptomatic knee osteoarthritis exhibited lower values compared to age-matched asymptomatic subjects. In addition, highly consistent speed-dependent increases in ELLIS outputs (in the asymptomatic subjects) were also documented. This speed-dependency is consistent with the fact that stable walking at a faster pace places higher demands on the neuromuscular control systems. Complex interactions across multiple controlling factors presumably increase perturbations to gait kinematics within the “normal” range (i.e., increase in physiological variability). To advance understanding of the degree of speed dependence, the present study aimed to test whether or not the ELLIS outputs would linearly increase with increase in walking speed.


A.S. Acker J.n-F. Fischer K. Aminian E. Martin B.M. Jolles

Summary Statment

The dual-mobility cup seems to bring more stability without changing the gait pattern.

Introduction

Dislocations and instability are among the worst complications after THA in elderly patient. Dual mobility cups seem to lower these risks. To our knowledge no study performed a gait analysis of dual cup in this group.


T. Flaxman A. Smith D. Benoit

Summary Statement

Using a weight-bearing force control task, age-related changes in muscle action were observed in osteoarthritic subjects, however, greater activation of rectus femoris and medial hamstring muscles in the OA group compared to control indicates greater cocontraction and varied stabilisation strategies.

Introduction

Osteoarthritis (OA) is the most debilitating condition among older adults. OA is thought to be mechanically driven by altering the stabilising integrity of the joint. The main contributor to knee joint stability is that of muscular contraction. In cases where the history of a traumatic knee joint injury is not a causal factor, a change in muscle function, resulting in reduced strength and force control in believed to induce OA development and progression. Since age is also a determining factor of OA, the purpose of this study was to investigate the muscle activation patterns of young healthy adults (YC), older healthy adults (OC), and adults with OA during a standing isometric force control task.


K. Iwamoto T. Tomita T. Yamazaki A. Sasaki Y. Kii K. Futai T. Miyamoto M. Fujii H. Yoshikawa K. Sugamoto

Summary

The effect of the geometry of the tibial polyethylene insert was investigated in vivo loaded conditions.

Introduction

The decision to choose CR (cruciate retaining) insert or CS (condylar stabilised) insert during TKA remains a controversial issue. Triathlon CS type has a condylar stabilised insert with an increased anterior lip that can be used in cases where the PCL is sacrificed but a PS insert is not used. The difference of the knee kinematics between CR and CS insert remains unclear. This study measured knee kinematics of deep knee flexion under load in two insert designs using 2D/3D registration technique.


M. Oosterwaal S. Telfer J. Woodburn A. Witlox J. Hermus L. van Rhijn K. Meijer

Summary Statement

An alternative way to assess three dimensional skin motion artefacts of kinematic models is presented and applied to a novel kinematic foot model. Largest skin motion is measured in the tarsal region.

Introduction

Motion capture systems are being used in daily clinical practise for gait analysis. Last decade several kinematic foot models have been presented to gain more insight in joint movement in various foot pathologies. No method is known to directly measure bone movement in a clinical setting. Current golden standard is based on measurement of motion of skin markers and translation to joint kinematics. Rigid body assumptions and skin motion artefacts can seriously influence the outcome of this approach and rigorous validation is required before clinical application is feasible. Validation of kinematic models is currently done via comparison with bone pin studies. However, these studies can only assess major bones in a highly invasive way; another problem is the non-synchronous measurement of skin markers and bone pins. Recently the Glasgow Maastricht kinematic foot model, which comprises all 26 foot segments, has been presented. To validate the model we propose a novel non-invasive method for the assessment of skin motion artefact, involving loaded CT data.


J. Arnold S. Mackintosh S. Jones D. Thewlis

Summary Statement

This study provides preliminary evidence that people with knee osteoarthritis have greater asymmetry in joint loading than healthy controls. Altered loading of the contralateral limb may signify increased risk of injury to other lower limb joints in knee osteoarthritis.

Introduction

Compensatory overloading of other lower limb joints is a potential reason for the non-random evolution of osteoarthritis (OA). In individuals with knee OA altered joint loading exists of the contralateral cognate joints. However, previous studies have neglected the temporal features of asymmetry in joint loading. The study aimed to identify the amount and temporal features of asymmetry in lower limb joint loading in advanced knee OA.


D. Crisan D.I. Stoia R. Prejbeanu M. Toth-Trascau D. Vermesan

Summary Statement

Objectifying postoperative recovery of patients with comminuted tibial plateau fractures treated with a unilateral plate trough the use of a gait analysis system.

Introduction

Gait analysis has been a proved method for assessing postoperative results in patients with different orthopedic afflictions of the lower limb such as hallux valgus, ankle instabilities, knee osteoarthritis and arthroplasties but it has rarely been used for postoperative assessment of proximal tibial fractures. The more traditional means of quantifying postoperative articular step-off and limb axis deviations such as conventional X Rays and CT scanning and the clinician and patient completed scores that subjectively assess the outcome are complemented by the analysis of gait patterns set to objectify the most important patient related factor - the gait. As controversy exists in literature regarding the optimal treatment for severe tibial plateau fractures we proposed a gait study to evaluate locked angle unilateral plate osteosynthesis.

Patient & Method: A computerised motion analysis system and a sensor platform were used to gather gait data from 15 patients with unilateral tibial plateau fractures graded Shatzker V and VI treated with a angular stable locked lateral plate osteosynthesis. Gait analysis was performed postoperatively based on patient availability and as soon as ambulation was possible and permitted without auxiliary support (crutches) at 4 (mean of 4,6), 6 (mean of 6,2) and 12 (mean of 11,7) months respectively, at a naturally comfortable walking. All patients were evaluated using classic anteroposterior and lateral knee radiography and were asked to fill the KOOS score questionnaire at the time of the gait analysis session.


R. Papalia G. Vadalà F. Franceschi E. Franceschetti B. Zampogna N. Maffulli V. Denaro

Introduction

Rotator cuff healing after an arthroscopic repair is discussible because of the high incidence of failures. Among biologic augmentations currently used, platelet-rich plasma (PRP) is one of the most applied, supposed to enhance and accelerate the healing process in different musculoskeletal disorders. However, the evidence supporting its successful administration is still lacking, especially in the field of the rotator cuff repair. Our purpose is to clarify if the recovery is accelerated and the integrity of repaired construct is increased in patients undergoing PRP injections after arthroscopic repair of the rotator cuff.

Patients & Methods

Thirty-eight patients with full-thickness rotator cuff tears have been enrolled after they had been informed about the use of PRP and the timing of its application postoperatively. Seventeen patients underwent arthroscopic rotator cuff repair and PRP injections (3 injections at 10 days each other), 21 underwent arthroscopic rotator cuff repair without PRP injections. Outcomes were assessed preoperatively, at 3, 6, 12, and minimum 16 months after surgery (average 17.7 +/− 1.7 months). Constant system, the University of California at Los Angeles (UCLA) system and a Visual Analogue Scale (VAS) scale were used; range of motion and strength in all planes were also assessed. The healing of the repair was assessed at magnetic resonance imaging at a minimum follow up of 6 months from surgery. All patients had the same rehabilitation protocol.


K. Hildebrand M. Zhang P. Salo D. Hart D. Befus

Summary

Previous work in a rabbit model of post-traumatic joint contractures shows that the mast cell stabilizer ketotifen decreases contracture severity. We show here that ketotifen decreases collagen gel contraction mediated by rabbit joint capsule fibroblasts when mast cells are present.

Introduction

Ketotifen was shown to decrease contracture severity and associated joint capsule fibrosis in an animal model of post-traumatic joint contractures. Ketotifen prevents the release of profibrotic growth factors from mast cells (MC). An in vitro collagen gel contraction assay is used to examine the effect of ketotifen on joint capsule fibroblasts obtained from this animal model.


R. Papalia G. Vadalà L. Moro F. Franceschi S. Vasta E. Albo A. Tecame N. Maffulli V. Denaro

Introduction

recent studies recognised metabolic abnormalities as additional factors in the development of rotator cuff (RC) tendinopathy. It has been hypothesised that the insertional area of this tendon is susceptible to degenerative changes due to intrinsic hypovascularization. The mechanisms underlying this process are not yet clear. In this study we attempted to confirm if larger lesions of the RC are related to impaired vasodilatatory response of the local circulation in conditions of “hemodynamic stress”.

Patients & Methods

it was assumed that impaired vasal reaction to “hemodynamic stress” was a systemic condition. This phenomenon should therefore be not limited to the critical area of the tendon tear. Given this assumption post-ischemic vasodilation of brachial artery was studied through an echo-doppler (US) evaluation. 50 patients (mean 61 ± 4, range 50–65) all scheduled for surgical rotator cuff repair following a tendon tear, were enrolled. Three preoperative measurements of the brachial artery diameter before and after application of an ischemic band were collected. The size of the lesions was later assessed at the time of surgery. A statistical analysis was carried on to investigate the correlation between US assessment of brachial artery diameter and the corresponding size of the RC lesions. UCLA and ASES scores were also measured to assess clinical and functional outcomes.


H. Razmjou R. Holtby

Summary

In the sample studied, reparability of large and massive tears was associated with pre-op ASES and active external rotation in neutral position. Surgical factors affecting reparability were tear size, tendon mobility and shape of the tear.

Introduction

The limited literature has shown good results with partial repairs of large and massive tears of rotator cuff but the role of factors that affect reparability is less clear 1-3. The purpose of this study was twofold, 1) to explore the predictive value of clinical and surgical factors on reparability of large and massive rotator cuff tears and 2) to examine the relationship between reparability and clinical and disability measures.


H. Razmjou G. Gunnis R. Holtby

Summary

Data of 663 patients with three different pathologies were examined. We found that using patients with significant symptoms and functional difficulty in the opposite shoulder will not bias the results of observational studies if outcomes are based on routine disability measures such as ASES or Constant-Murley scores.

Introduction

Recently, using patients with bilateral limb problems as independent cases has raised concerns in orthopaedic research due to violating the assumption of independence. If observations are too similar in characteristics, they become highly correlated which leads to lowering the variance and biasing the results. Type of pathology (impingement, cuff tear, osteoarthritis) and aging are expected to affect the incidence of bilateral shoulder complaints and should be considered when examining potential bias in this area. In addition, the impact of dominant side pathology has not been investigated primarily in patients with shoulder problems. The objectives of this study were: 1) to examine the incidence of bilateral shoulder complaints and pathology on the dominant side in patients with impingement syndrome, rotator cuff tear and osteoarthritis of the glenohumeral joint, 2) to explore the role of sex and age in developing bilateral shoulder complaints, and 3) to examine the impact of bilaterality and hand dominance on pre and one year post-operative disability.


R. Dhir S. Lambert

Summary Statement

Sprengel's deformity is a rare congenital anomaly, with scapula malposition. We present a unique subgroup of Sprengel's possessing a cleithrum, an ancestral remnant of shoulder-girdle development found in bony-fish. This challenges management providing valuable insight into scapular embryology and development.

Introduction

Sprengel's deformity is a rare congenital anomaly of the shoulder girdle characterised by scapula malposition, associated with atrophy of periscapular muscles causing disfigurement and limited shoulder movement. Traditionally, it has been managed by omovertebral bar excision and muscle transplantation procedures guided by age and Cavendish grading. We present a unique, previously undescribed observation in humans: a case series of patients with Sprengel's deformity possessing a cleithrum, an ancestral remnant of shoulder-girdle development found in archaic bony fish.


H. Razmjou P. Henry T. Dwyer R. Holtby

Summary

Analysis of existing data of patients who had undergone debridement procedure for osteoarthritis (OA) of glenohumeral joint showed improvement in disability at a minimum of one year following surgery. Injured workers were significantly younger and had a poorer outcome.

Introduction

There is little information on debridement for OA of the shoulder joint. The purpose of this study was to examine factors that affect the outcome of arthroscopic debridement with or without acromioplasty /resection of clavicle of patients with osteoarthritis of the glenohumeral joint, in subjective perception of disability and functional range of motion and strength at a minimum of one year following surgery.


K. Zheng C. Scholes J. Lynch D. Parker Q. Li

Summary Statement

An MRI-derived subject-specific finite element model of a knee joint was loaded with subject-specific kinetic data to investigate stress and strain distribution in knee cartilage during the stance phase of gait in-vivo.

Introduction

Finite element analysis (FEA) has been widely used to predict the local stress and strain distribution at the tibiofemoral joint to study the effects of ligament injury, meniscus injury and cartilage defects on soft tissue loading under different loading conditions. Previous studies have focused on static FEA of the tibiofemoral joint, with few attempts to conduct subject-specific FEA on the knee during physical activity. In one FEA study utilising subject-specific loading during gait, the knee was simplified by using linear springs to represent ligaments. To address the gap that no studies have performed subject-specific FEA at the tibiofemoral joint with detailed structures, the present study aims to develop a highly detailed subject-specific FE model of knee joint to precisely simulate the stress distribution at knee cartilage during the stance phase of the gait cycle.


A. Carriero M. Vogt S. Shefelbine

Summary

Canals are the preferential sites for failure in cortical bone and their architecture is able to dictate the mechanical behaviour of the bone: smaller and branched canals generate a high volume of bone failure even at low apparent tissue strain.

Introduction

Osteogenesis imperfecta (OI), or brittle bone disease, is caused by mutations in the collagen genes and results in skeletal fragility. We recently showed that a mouse model of osteogenesis imperfecta (oim) has smaller and denser intracortical canals with a branched architecture compared to healthy wild type (WT) bones with similar cortical porosity [1]. We hypothesise this abnormal intracortical structure contributes to the increased fracture risk of the oim bones.


J. Sultan G. Chapman R. Jones

Summary

This study shows a significant reduction in knee adduction moment in patients with medial compartment osteoarthritis, in both the symptomatic and asymptomatic knees. Long-term follow-up studies are required to confirm the effect of treating the asymptomatic side on disease progression.

Background

The knee is the commonest joint to be affected by osteoarthritis, with the medial compartment commonly affected. Knee osteoarthritis is commonly bilateral, yet symptoms may initially present unilaterally. Higher knee adduction moment has been associated with the development and progression of medial compartment knee osteoarthritis. The aim of this study was to assess the effect of lateral wedge insoles on the asymptomatic knee of patients with unilateral symptoms of medial compartment knee osteoarthritis.


A. Speirs H. Frei M. Lamontagne P. Beaule

Summary

The cartilage layer from cam-type femoroacetabular impingement deformities had lower stiffness and increased permeability compared to normal cartilage. This is consistent with osteoarthritis and supports the hypothesis of abnormal contact stresses.

Introduction

Femoroacetabular impingement (FAI) has recently been associated with osteoarthritic (OA) degeneration of the hip and may be responsible for up to 90% of adult idiopathic OA cases. FAI results from deformities in the hip joint which may lead to abnormal contact stresses and degeneration. The more common cam-type deformity consists of a convex anterior femoral head-neck junction which impinges the anterosuperior acetabular rim during flexion and internal rotation of the hip. Increased subchondral bone density has been reported in this region which may be a bone remodelling response to increased contact stress. The abnormal contact is expected to cause degeneration of the cartilage layer. The goal of this study was to assess the mechanical properties of cartilage retrieved from the cam deformity and to compare this with normal articular cartilage from the femoral head. It is hypothesised that the cartilage will have a lower elastic modulus and higher permeability than normal cartilage.


A. Bou Francis N. Kapur R.M. Hall

Summary Statement

There are no standardised methods for assessing the cement flow behaviour in vertebroplasty. We propose a novel methodology to help understand the interaction of cement properties on the underlying displacement of bone marrow by bone cement in porous media.

Introduction

Concerns related to cement extravasation in vertebroplasty provide the motivation for the development of methodologies for assessing cements (novel and commercially available) and delivery systems. Reproducible and pathologically representative three-dimensional bone surrogates are used to understand the complex rheology underlying the two-phase flow in porous media.


I. Zderic M. Windolf B. Gueorguiev V. Stadelmann

Summary

Time-lapsed CT offers new opportunities to predict the risk of cement leakage and to evaluate the mechanical effects on a vertebral body by monitoring each incremental injection step in an in-vitro vertebroplasty procedure.

Introduction

Vertebroplasty has been shown to reinforce weak vertebral bodies and to prophylactically reduce fracture risks. However, bone cement leakage is a major vertebroplasty related problem which can cause severe complications. Leakage risk can be minimised by injecting less cement into the vertebral body, inevitably compromising the mechanical properties of the augmented bone, as a proper endplate-to-endplate connection of the injected cement is needed to obtain a mechanical benefit. Thus the cement flow in a vertebroplasty procedure requires a better understanding. This study aimed at developing a method to monitor the cement flow in a vertebral body and its mechanical effect.


C. Hydorn K. Nathe M. Kanwisher J.D. DesJardins M. Rogers A. Bertram

Summary Statement

This study examined the fixation stiffness of 13 tibial and 12 femoral Salter-Harris fracture fixation methods, and determined that screws and screws+ k-wires methods provided the highest stability. In situations where k-wire use is unavoidable, threaded k-wires are preferable.

Introduction

Salter-Harris fractures of the proximal tibia and distal femur are common in pediatric patients that present to orthopedic surgeons. Salter-Harris type I fractures are characterised by breaks that extend only through the physis while Salter-Harris II fractures are the most common, accounting for 85% of Salter-Harris fractures, and extend past the growth plate, exiting through the metaphyseal bone. Fixation of these fracture types can be accomplished using a variety of methods including the use of Kirschner wires, cannulated screws, and a combination of both materials. Stability of fracture fixation is of utmost importance as persistent motion at the fracture margin leads to deformity. The purpose of this study is to analyze the biomechanical efficacy of various fixation methods used to stabilise Salter-Harris I and II fracture patterns in both the proximal tibia and distal femur. Stiffness, the primary gauge of efficacy, will be tested in flexion and extension, varus and valgus movement, and internal and external rotation and will be compared to determine the optimal fixation method.


F. Amirouche G. Solitro M. Gonzalez

Summary Statement

A FEA model built from CT-data of frozen cadaver has been validated and used for under-reaming experiments. 1 mm under-reaming can provide contact surface and micromotions that are acceptable and within the clinical relevance without high impact force.

Introduction

Long-term cup fixation and stability in total hip arthroplasty (THA) is directly related to the bone ingrowths between the porous cup and the acetabulum. To achieve the initial cup setting, 1 mm of under reaming is becoming the gold standard for cementless cup and what is at stake is usually the actual contact between cup and acetabulum wall. During impact and cup placement, friction forces are generated from the “not permanent” deformations of the acetabular wall that are translated into a gap between the reamed bone and the cup. Clinically the surgeon objective is to have the gap extended to a limited portion of the cup in order to improve bone ingrowth. Hence, the need arises from examining this cup bone stability interface by examining the selected “under reaming” conditions, the surface of contact between the acetabular cup and the bone and its relation to the impact force resulting from the hammering of the cup.


C. Falcinelli E. Schileo L. Balistreri F. Baruffaldi A. Toni U. Albisinni F. Ceccarelli L. Milandri M. Viceconti F. Taddei

Summary Statement

In a retrospective study, FE-based bone strength from CT data showed a greater ability than aBMD to discriminate proximal femur fractures versus controls.

Introduction

Personalised Finite Element (FE) models from Computed Tomography (CT) data are superior to bone mineral density (BMD) in predicting proximal femoral strength in vitro [Cody, 1999]. However, results similar to BMD were obtained in vivo, in retrospective classification of generic prevalent fractures [Amin, 2011] and in prospective classification of femoral fractures [Orwoll, 2009]. The aim of this work is to test, in a case-control retrospective study, the ability of a different, validated FE modelling procedure [Schileo, 2008] to: (i) discriminate between groups of proximal femoral fractures and controls; (ii) individually classify fractures and controls.


S.R. Moore G. Saidel M.L. Knothe Tate

Summary Statement

A coupled finite element - analytical model is presented to predict and to elucidate a clinical healing scenario where bone regenerates in a critical-sized femoral defect, bounded by periosteum or a periosteum substitute implant and stabilised via an intramedullary nail.

Introduction

Bone regeneration and maintenance processes are intrinsically linked to mechanical environment. However, the cellular and subcellular mechanisms of mechanically-modulated bone (re-) generation are not fully understood. Recent studies with periosteum osteoprogenitor cells exhibit their mechanosensitivity in vitro and in situ. In addtion, while a variety of growth factors are implicated in bone healing processes, bone morphogenetic protein-2 (BMP-2) is recognised to be involved in all stages of bone regeneration. Furthermore, periosteal injuries heal predominantly via endochondral ossification mechanisms. With this background in mind, the current study aims to understand the role of mechanical environment on BMP-2 production and periosteally-mediated bone regeneration. The one-stage bone transport model [1] provides a clinically relevant experimental platform on which to model the mechanobiological process of periosteum-mediated bone regeneration in a critical-sized defect. Here we develop a model framework to study the cellular-, extracellular- and mechanically-modulated process of defect infilling, governed by the mechanically-modulated production of BMP-2 by osteoprogenitor cells located in the periosteum.


S. Zulqadar S.H. McBride U. Knothe M.L. Knothe Tate

Summary Statement

The purpose of this experimental imaging study is to determine the Poisson's ratio of ovine periosteum, using strain mapping data from an imaging study designed to elucidate the mechanical environment of periosteal progenitor cells in situ during stance shift loading.

Introduction

Periosteum is a composite, so-called “smart” or stimuli responsive material that provides a niche for pluripotent cells that exhibit mechanosensitivity in their proliferative and differentiation behavior. The overarching aim of this research program is to explore, understand, and exploit the mechanical signals that promote cell lineage commitment and de novo bone generation during embryonic development and postnatal healing. Further, our working hypothesis is that periosteum derived progenitor cells are highly sensitive to their local mechanical milieu, which guides their proliferation, motility and differentiation behavior. As a first step toward understand the role of periosteum anisotropy on defining the local mechanical milieu of a given progenitor cell, the objective of the current study is to determine the Poisson's ratio of ovine periosteum and its sensitivity to near, mid- and long-range strains.


S.R. Moore S. Milz M.L. Knothe Tate

Summary Statement

Thickness and cellularity of human periosteum are important parameters both for engineering replacement tissue as well as for surgeons looking to minimise tissue damage while harvesting the most viable periosteum possible for autologous regenerative therapies. This study provides a new foundation for understanding the basic structural features of middiaphyseal periosteum from femora and tibiae of aged donors.

Introduction

A number of recent studies describe mechanical, permeability and regenerative properties of periosteal tissue and periosteum derived cells in a variety of animal models [1,2]. However, due to lack of access in healthy patients, the structural properties underlying human periosteum's inherent regenerative power and advanced material properties are not well understood. Periosteum comprises a cellular cambium layer directly apposing the outer surface of bone and an outer fibrous layer encompassed by the surrounding soft tissues. As a first step to elucidate periosteum's structural and cellular characteristics in human bone, the current study aims to measure cambium and fibrous layer thickness as well as cambium cellularity in human femora and tibiae of aged donors.


T. Wang F. Yang J. Lai

Summary Statement

We have developed 3D combinatorial hydrogels containing cartilage extracellular matrix (ECM) proteins for modulating chondrogenesis of adipose-derived stromal cells. Our platform allows independently tunable biochemical and mechanical properties, which may provide a valuable tool for elucidating how ECM biochemical cues interact with matrix stiffness to regulate stem cell chondrogenesis.

Introduction

Adipose-derived stromal cells (ADSC) hold great promise for cartilage repair given their relative abundance and ease of isolation. Biomaterials can serve as artificial niche to direct chondrogenesis of ADSCs, and extracellular matrix (ECM) protein-based scaffolds are highly biomimetic. However, incorporating ECM molecules into hydrogel network often lead to simultaneous changes in both biochemical ligand density and matrix stiffness. This makes it difficult to understand how various niche signals interact together to regulate ADSC fate. To overcome these limitations, the goal of this study is to develop an ECM-containing hydrogel platform with independently tunable biochemical and mechanical cues for modulating ADSC chondrogenesis in 3D. We hypothesise that decreasing the degree of crosslinking of ECM molecules may allow their incorporation without affecting the matrix stiffness. The effects of interactive signaling between ECM molecules and matrix stiffness on ADSC chondrogenesis in 3D was then examined using this platform


M. Sladkova M. Manassero V. Myrtil H. Savari M. Fall D. Thomas M. Bensidhoum D. Logeart-Avramoglou H. Petite

Introduction

The use of mesenchymal stem cells (MSCs) loaded on osteoconductive scaffolds has emerged as a potential new treatment of large bone defects but has generated marginally successful results in terms of new bone formation. It is supposed that MSC massive death post implantation is a major obstacle for the exhibition of their osteogenic potential. Yet, the very few studies conducted using primary human MSCs derived from bone marrow (hMSCs), a clinically pertinent cell source, did not demonstrate that cell survival is required for new bone formation. In order to elucidate whether cell survival is needed for hMSC to express their osteogenic potential, the present study examined in an ectopic mouse model the relationship between cell survival and osteogenic potential of hMSCs loaded onto osteoconductive scaffold.

Materials and Methods

hMSCs (106) were seeded on 40-mg calcium carbonate (Biocoral) particles (size: 610–1000 µm), wrapped in fibrin gel (Baxter), and implanted subcutaneously into immunodeficient (nu/nu) mice (n=8/group). The fate of implanted cells was analysed using the bioluminescence and immunohistochemistry. For this, hMSCs were transduced with Luc-GFP (Luciferase-Green fluorescent protein) lentiviral vectors prior to experimentation. Bone formation was analysed 8 weeks post implantation on both non-decalcified and decalcified samples.


C. Scotti E. Piccinini H. Takizawa A. Todorov P. Bourgine A. Papadimitropoulos A. Barbero M.G. Manz I. Martin

Summary Statement

This study reports that hMSC can be manipulated in order to engineer a bone organ, characterised by mature osseous and vascular components and capable to recruit, host and maintain functional HSCs.

Introduction

Bone tissue engineering strategies are typically based on methods involving adult human Mesenchymal Stromal Cells (hMSC) in a process resembling intramembranous ossification. However, most bones develop and repair through endochondral ossification. In addition, endochondral ossification presents several advantages for regenerative purposes such as osteogenic activity, capability to drive formation of the Hematopoietic Stem Cell (HSC) niche, resistance to hypoxia, intrinsic vasculogenic potential and, consequently, efficiency of engraftment. In this study, we aimed at developing an endochondral bone organ model characterised by functional osseous and hematopoietic compartments by using hMSC.


N. Tovar M. Sobieraj L. Witek J. Smay P. Coelho

Summary

A specialised 3D- printed scaffold, combined with fillers and bioactive molecules, can be designed and characterised to demonstrate the efficacy of synthetic, off-the-shelf and custom fabricated scaffolds for the repair of long bone defects.

Introduction

Using specialised three-dimensional (3-D) printing technology, combined with fillers and bioactive molecules, 3-D scaffolds for bone repair of sizable defects can be manufactured with a level of design customization that other methods lack. Hydroxyapatite (HA)/Beta-Tri-Calcium Phosphate (β -TCP) scaffold components may be created that provide mechanical strength, guide osseo- conduction and integration, and remodel over time. Additionally, research suggests that bone morphogenic protein (BMP) stimulates growth and differentiation of new bone. Therefore, we hypothesise that with the addition of BMP, HA- β -TCP scaffolds will show improved regeneration of bone over critical sized bone defects in an in vivo model.


M. Poldervaart H. Gremmels K. van Deventer J. Fledderus F. Cumhur Oner M. Verhaar W. Dhert J. Alblas

Summary Statement

Prolonged presence of VEGF (released from gelatin microspheres) led to a significant increase in scaffold vascularization when applied in vivo. Bioprinted scaffolds with regional VEGF presence retained their architecture and regional vessel formation occurred.

Introduction

Tissue-engineered bone constructs need timely vascularization for optimal performance in regeneration. A potent stimulus of vascularization is vascular endothelial growth factor (VEGF), a factor with a short half-life time. Controlled release of VEGF from gelatin microparticles (GMPs) was investigated as a means to prolong VEGF presence at the preferred location within bioprinted scaffolds, and study subsequent vascularization.


A. Malhotra M. Pelletier Y. Yu C. Christou W.R. Walsh

Summary Statement

An autologous thrombin activated 3-fold PRP, mixed with a biphasic calcium phosphate at a 1mL:1cc ratio, is beneficial for early bone healing in older age sheep.

Introduction

The management of bone defects continues to present challenges. Upon activation, platelets secrete an array of growth factors that contribute to bone regeneration. Therefore, combining platelet rich plasma (PRP) with bone graft substitutes has the potential to reduce or replace the reliance on autograft. The simple, autologous nature of PRP has encouraged its use. However, this enthusiasm has failed to consistently translate to clinical expediency. Lack of standardisation and improper use may contribute to the conflicting outcomes reported within both pre-clinical and clinical investigations. This study investigates the potential of PRP for bone augmentation in an older age sheep model. Specifically, PRP dose is controlled to provide clearer indications for its clinical use.


D. Lozano A. López-Herrradón S. Portal-Núñez J.A. Ardura M. Vila S. Sánchez-Salced F. Mulero E. Gómez-Barrena M. Vallet-Regí P. Esbrit

Summary Statement

Parathytorid hormone-related protein (107–111) loaded onto biopolymer-coated nanocrystalline hydroxyapatite (HAGlu) improves the bone repair in a cavitary defect in rat tibiae.

Introduction

Biopolymer-coated nanocrystalline hydroxyapatite (HAGlu) made as macroporous foams are promising candidates as scaffolds for bone tissue engineering applications. They exhibit optimal features, promoting internalization, proliferation and differentiation of osteoprogenitors, with an adequate cell colonization over the entire scaffold surface. Parathyroid hormone-related protein (PTHrP) is an important modulator of bone formation. Its 107–111 epitope (osteostatin) exhibits osteogenic properties at least in part by directly acting on osteoblasts. The main aim of this study was to evaluate whether osteostatin loading into HAGlu scaffolds might improve their bone regeneration capacity.


A. Marmotti F. Castoldi R. Rossi M. Bruzzone F. Dettoni S. Marenco D.E. Bonasia D. Blonna M. Assom C. Tarella

Summary Statement

Preoperative bone-marrow-derived cell mobilization by G-CSF is a safe orthopaedic procedure and allows circulation in the blood of high numbers of CD34+ve cells, promoting osseointegration of a bone substitute.

Introduction

Granulocyte-colony-stimulating-factor(G-CSF) has been used to improve repair processes in different clinical settings for its role in bone-marrow stem cell(CD34+ and CD34-) mobilization. Recent literature suggests that G-CSF may also play a role in skeletal-tissue repair processes. Aim of the study was to verify the feasibility and safety of preoperative bone-marrow cell (BMC) mobilization by G-CSF in orthopaedic patients and to evaluate G-CSF efficacy in accelerating bone regeneration following opening-wedge high tibial valgus osteotomy(HTVO) for genu varum.


R. Lerf R.P. Badertscher C. Adlhart D. Delfosse

Summary Statement

In the most recent type of highly cross-linked UHMWPE, stabilised by vitamin E, the majority of this anti-oxidant cannot be leached out. Even more, the vitamin E molecules are grafted to the UHMWPE polymer backbone by an ether bond.

Introduction

Today, highly cross-linked, vitamin E stabilised UHMWPE is clinically accepted as bearing material in joint replacements. Little is known about the chemistry of this antioxidant in the polymer after irradiation. The present investigation presents a model for the chemical nature of the trapping of vitamin E in PE.


R. Lerf D. Delfosse

Summary Statement

In the present hip simulator studies, bearings with the newest generation of HXLPE, stabilised with vitamin E, did not show increased wear under severe conditions, such as accelerated ageing, component mal-orientation and third body wear.

Introduction

Unfortunately, acetabular hip components cannot always be implanted in optimal condition. Therefore, we performed hip simulator studies with cups made from highly cross-linked, vitamin E stabilised UHMWPE in i) artificially aged condition, ii) with an inclination angle corresponding to 80 ° in vivo and iii) with third bodies coming from the Ti coating of the acetabular cup.


E. Oral A. Neils B. Doshi O. Muratoglu

Summary

Low energy irradiation of vitamin E blended UHMWPE is feasible to fabricate total joint implants with high wear resistance and impact strength.

Introduction

Irradiated ultra-high molecular weight polyethylene (UHMWPE), used in the fabrication of joint implants, has increased wear resistance. But, increased crosslinking decreases the mechanical strength of the polymer, thus limiting the crosslinking to the surface is desirable. Here, we used electron beam irradiation with low energy electrons to limit the penetration of the radiation exposure and achieve surface cross-linking.


S. Rowell C. Reyes H. Malchau O. Muratoglu

Summary

Four highly cross-linked UHWMPEs except vitamin E-stabilised explants

Introduction

The development of both first and second generation highly cross-linked material focused on stabilizing radiation-induced free radicals as the sole precursor to oxidative degradation; however, secondary in vivo oxidation mechanisms have been identified in both conventional and highly cross-linked UHMWPE, induced by absorbed lipids and cyclic mechanical load. Retrieval studies are reporting in vivo oxidation highly cross-linked retrievals with up to ten year in vivo durations. Preclinical aging tests did not predict these in vivo material changes. With only a decade of these materials in clinical use, retrieval studies are limited to mid-term follow-up. In vitro studies face a challenge in effectively replicating the precise in vivo conditions that lead to this loss of oxidation resistance. In this study, we bypass replicating these in vivo variables by examining surgically-retrieved components, thereby testing material that has been affectively “pre-conditioned” by their in vivo service. After a preliminary post-operative analysis, we subjected retrievals to accelerated aging tests in order to predict the extent to which their oxidative stability had been uniquely compromised in vivo.


S. Rowell D. Estok S. Kreuzer H. Malchau O. Muratoglu

Summary

Sequentially irradiated and annealed UHMWPE hip and knee retrievals showed subsurface in vivo oxidation in both the articular surface and unloaded surfaces, while three of four never-implanted shelf stored liners had oxidation in the bulk.

Introduction

Highly cross-linked polyethylene was developed to improve the wear resistance of UHMWPE bearing surfaces in total hip arthroplasty. First generation irradiated and annealed polyethylene showed high oxidation in vivo, largely attributed to only the partial-quenching of free radicals, along with additional radicals generated during terminal gamma sterilization. A second generation, three-step sequential irradiation and annealing method was advanced with the promise of better oxidative stability and improved mechanical properties. We hypothesised that without the complete elimination of free radicals combined with gas plasma sterilization requiring oxygen-permeable packaging, that this second generation material would be prone to shelf-oxidation in addition to in vivo oxidation.


S. Rowell O. Muratoglu

Summary

Fifteen irradiated, vitamin E-diffused UHMWPE retrievals with up to three years in vivo service showed no appreciable oxidation, nor change in material properties from a never-implanted liner, and showed a 94% decrease in free radical content.

Introduction

Radiation cross-linking, used to improve wear resistance of ultra-high molecular weight polyethylene (UHMWPE) bearings used in total joint arthroplasty, generates residual free radicals which are the precursors to oxidative embrittlement. First generation materials adopted thermal treatments to eliminate or reduce free radical content, but came with compromises in reduced mechanical properties or insufficient stabilization. A second generation alternative method infuses an antioxidant, vitamin E, into irradiated UHMWPE to stabilise free radicals while maintaining fatigue strength. In vitro studies predict excellent oxidation and wear resistance in vitamin E-stabilised bearings, but the long-term in vivo oxidation behavior, influenced by lipid absorption and cyclic loading, remains largely unknown. Our aim was to investigate in vivo changes in UHMWPE surgically-retrieved explants that were radiation cross-linked and stabilised by vitamin E.


A. Drynda G. Singh G. Buchhorn S. Kliche B. Feuerstein M. Ruetschi C. Lohmann

Summary Statement

CXCR4 gene and protein expression is regulated in a dose and time-dependent manner by metallic wear debris but not polyethylene wear debris in vitro and in vivo.

Introduction

Progressive osteolysis leading to aseptic loosening among metal-on-metal (MoM) total hip arthroplasties (THA's), and adverse reactions to metallic debris (ARMD) are increasing causes for concern among existing patients who have been implanted with MoM hip replacements. Close surveillance of these patients is necessary and difficulties lie in early detection as well as differentiating low-grade infection from ARMD in the early stages. Several inflammatory markers have been investigated in this context, but to date, none is specific with regards to the offending material. In earlier studies, it has been shown that osteoblastic phenotypes and differentiation are regulated by different types of wear particles.


K. Yeung Y. Zhao P. Li Z. Xu P. Chu

Summary Statement

3D porous and nano-structured polyetheretherketone (PEEK) surface embedded with biofunctional groups can not only induce the up-regulation of osteogenic genes and proteins in-vitro, but also help promote new bone formation in-vivo.

Introduction

Porous biomaterials with three-dimensional (3D) surface structure can enhance biological functionalities especially in bone tissue engineering. Many techniques have hitherto been utilised to fabricate porous structures on metal surfaces, including machining, shotblasting, anodic oxidation, alkali treatment and acid-etching. However, it has been difficult to accomplish this on polyetheretherketone (PEEK) due to its inherent chemical inertness. In this study, we have applied a method comprising of sulfonation and water immersion to establish a 3D porous and nanostructured network on the PEEK surface. This newly established 3D network embedded with bio-functional groups can help promote new bone formation in-vivo.


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V. Senthilkumar S. Goel K.K. Gupta

Introduction

Stem cells have the capacity for self renewal and capability of differentiation into various cell lineages. Non union remains a clinically important problem in orthopaedic surgery.

Method

We randomly assigned 45 patients into 3 groups. Test group: 15 patients in which mesenchymal stem cells prepared by conventional density-gradient centrifugation using ficoll-hypaque solution were injected (n=15), control A: 15 patients in which autogenous bone marrow aspirate were injected (n=15), control B: 15 patients in which neither the stem cell nor bone marrow injection given, symptomatically treated(n=15). Ultra sound and x rays were performed at follow up of 6, 12, 18, 24 weeks and comparison done.


B. He J. Liu T. Tang B. Guo X. Pan A. Lu G. Zhang

Summary

We compare the difference in expression profiles of miRNAs during fracture healing between adult and aged female mice. This study reveals the possibility to improve impaired fracture healing in aged females by regulating key miRNAs at early stage.

Introduction

Impaired fracture healing in aged female skeleton is still a clinical challenge (Holroyd et al., Best Pract Res Clin Endocrinol Metab, 2008, Virk, Lieberman, Arthritis Res Ther, 2012). Angiogenesis and osteogenesis are the two key stages during fracture healing, which are impaired in aged female (Naik et al., J Bone Miner Res, 2009). MicroRNAs (miRNAs) are key post-transcriptional non-coding regulators of gene expression, which has demonstrated important roles in angiogenesis and osteogenesis (Bae et al., Hum Mol Genet, 2012, Plummer et al., Cancer Res, 2013). Understanding how non-coding regulatory RNA in fracture healing changes with age will help identifying novel therapeutic targets that can be exploited to improve fracture healing in the aged females.


S. Goel S. Sinha

Introduction

Amino acids like arginine and lysine have been suggested to hasten the process of fracture healing by improving the local blood supply, supplementing growth factors, and improving collagen synthesis. We studied the role of lysine and arginine in the fracture repair process with regard to the rate of healing, probable mechanisms involved in the process, and mutual synergism between these agents.

Materials and methods

In an experimental study, 40 rabbits were subjected to ulnar osteotomy. They were distributed in control (14) and test groups (26). Twenty-six animals in the test group were fed with a diet rich in lysine and arginine. Both the groups were followed radiologically and histologically till union.


M. Ishikawa H. Ito H. Yoshitomi K. Murata H. Shibuya M. Furu T. Kitaori T. Nakamura S. Matsuda

Summary Statement

MCP-1/ CCR2 axis at the early phase plays a pivotal role in the fracture healing. Inflammation plays a pivotal role in fracture healing. Among them, chemokines play key roles in inflammation. Monocyte chemotactic protein-1 (MCP-1), via its receptor C-C chemokine receptor 2 (CCR2), acts as a potent chemoattractant for various cells to promote migration from circulation to inflammation site. Thus, the importance of MCP-1/CCR2 axis in fracture healing has been suggested. However, the involvement of MCP-1/CCR2 axis tofracture site is not fully elucidated.

Results

PCR Array: The expression of MCP-1 and MCP-3 had increased on day 2 than 0 or 7 in the rib fracture healing. Immunohistochemistry Staining: To verify the localization of MCP-1 expression, we examined the Wild type (WT)-mouse rib fracture healing. We observed high expression of MCP-1 and MCP-3 at the periosteum and the endosteum on post-fracture day 3. In vivo Antagonist Study: To elucidate whether MCP-1/CCR2 axis is involved during the early phase of fracture healing, we continuously administered RS102895, CCR2 antagonist, before or after rib fracture. Micro-CT analysis showed delayed fracture healing in the before-group compared with both the control and after-group. On day 21, the hard callus volume in the before-group was significantly smaller than that in the control-group. Histological analysis showed that fractures in both the control and the after-groups were healed by day 21. In contrast, less of cartilage in the callus was observed in the before-group on day 7. Gain of Function: To examine the roles of MCP-1 at the periosteum and the endosteum during the fracture healing, we created a segmental bone graft exchanging model. The bone grafts were transplanted from MCP-1−/− mice to another MCP-1−/− mice (KO-to-KO). Micro-CT analysis showed that KO-to-KO transplantation led to the delay of fracture healing on day 21. Next, we created exchanging-bone graft models between MCP-1−/− and WT mice, in which a segmental bone derived from a WT mouse was transplanted into a host MCP-1−/− mouse (WT-to-KO). In contrast to KO-to-KO bone graft transplantation, the transplantation of WT-derived graft into host KO mouse resulted in a significant increase of new bone formation on day 21. Histological analysis revealed that marked and localised induction of MCP-1 expression in the periosteum and the endosteum around the WT-derived graft was observed in the host MCP-1−/− mouse. Loss of Function: To validate whether MCP-1 is a crucial chemokine for fracture healing, we created WT-to-WT and KO-to-WT bone graft models. When WT-donor graft was transplanted into WT-host, abundant new bone formation was observed around a WT-derived graft on day 21. In contrast, transplantation of KO-derived graft into WT-host resulted in a marked reduction of periosteal bone formation on a donor graft.


Y. Mori D. Rowe D. Adams E. Itoi

Summary Statement

The Dkk3-derived cells represent a branch of the periosteal mesenchymal lineage that produces fibrocartilage as well as regenerating the periosteal structures.

Introduction

Mesenchymal progenitor cells are capable of generating a wide variety of mature cells that constitute the connective tissue system. Our Laboratory has been developing SMAA GFP reporter mice to prove to be an effective tool for identifying these cells prior to the expression of markers of differentiation characteristic of bone, fat, muscular blood vessels or fibrocartilage. Dkk3 was chosen as a candidate reporter because microarray of SMAA-sorted cells culture indicated high expression of this non-canonical anti-Wnt factor, which was not anticipated in a culture with strong osteogenic potential.


R. Tomlinson K. Shoghi M. Silva

Summary Statement

Bone stress fracture triggers a rapid increase in blood flow in association with mast cell production of inducible nitric oxide synthase (iNOS). NOS inhibition blocks the increase in blood flow and reduces woven bone formation needed for stress fracture healing.

Introduction

Vascular-bone interactions are critical in skeletal development and fracture healing. We recently showed that angiogenesis is required for stress fracture healing. However, the changes in vascularity that occur in the first 72 hours after stress fracture can not be explained by angiogenesis. Here, we evaulated early changes in blood flow and vasodilation after either damaging (stress fracture) or non-damaging mechanical loading in rats.


P.K. Suen Y.-X. He D.H.K. Chow L. Huang C.-Y. Li H.Z. Ke L. Qin

Summary Statement

This study demonstrated that Sclerostin monoclonal antibody (Scl-Ab) enhanced bone healing in the rat osteotomy model. Scl-Ab increased callus size, callus bone volume fraction, rate of callus bone formation and fracture callus strength.

Introduction

Sclerostin is a protein secreted by osteocytes and is characterized as a key inhibitor of osteoblast-mediated bone formation. Previous studies demonstrated that treatment with a sclerostin monoclonal antibody (Scl-Ab) results in significantly increased bone formation, bone mass and strength in rat closed fracture model (1–2). However, the effects of Scl-Ab on healing of open fracture model have not yet been reported in rats. Previously in ORS and ASBMR Annual Meeting, we have reported that Scl-Ab promoted the open fracture healing at week 3 and week 6 post-fracture. Here we extended our investigation for up to week 9 with additional histological assessments and dynamic histomorphometric analysis to investigate the effects of systemic administration of Scl-Ab on a later phase of fracture repair.


W. Gao L. Cheng J. Dai H. Yang Q. Shi

Summary Statement

Collagen scaffolds modified with collagen-binding bFGF promotes the neural regeneration in the rat hemisected spinal cord injury model.

Objective

To investigate the effects of the collagen scaffolds (CS) combined with collagen-binding basic fibroblast growth factor (CBD-bFGF) on the neural recovery after spinal cord injury (SCI).


T. McIff K. Colbert A. Boyer A. Goodyear D. Mar

Summary Statement

A porcine model using Yucatan minipigs was found to be very promising for the investigation of healing around transcutaneous osseointegrated implants. Pigs demonstrated surprising agility and adaptability including the ability to ambulate on three legs during the immediate postoperative period.

Introduction

Previous non weight-bearing and weight-bearing caprine, canine and ovine models have evaluated design, material, and biological coating variations in an attempt to improve the wound healing and skin-implant seal around transcutaneous osseointegrated implants. Although these models have primarily been used as a window into the application of transcutaneous osseointegrated implants in humans, some important model characteristics affecting wound healing and infection have been missing including: 1) replication of the physiological tissue response, and 2) availability of a transcutaneous site with sufficient soft tissue coverage. Pig skin, like human, is relatively hairless, tightly attached to the subcutaneous tissue, vascularised by a cutaneous blood supply, and healed by means of epithelialization. Swine have been extensively utilised for superficial and deep wound healing studies and can offer ample soft tissue coverage following a lower limb amputation. Development of a porcine model is important for continued understanding and improvement of weight-bearing transcutaneous osseointegration.


C. Christou J. Rawlinson G. Mitchell R. Oliver W. Walsh

Summary

Timing for the application and use of fentanyl patches for pre-emptive analgesia and sedation is crucial to obtain good clinical outcomes. Placement and timing is important to maximise clinical effect and apparent levels of analgesia.

Introduction

The use of sheep as preclinical models for the investigation of orthopaedic conditions is gaining momentum, the control of their pain is a significant ethical issue. The daily need for injecting non-steroidal anti-inflammatory drugs (NSAIDs) and/or the shorter acting opioids increases the demand for handling post-operatively which can increase animal distress and risk of human injury. NSAIDs can have a negative effect on bone healing, complicating results. Opioid analgesics have no impact on bone healing. Fentanyl patches have become another option for use in pain management. Pre-emptive analgesia helps reduce the demand on post-operative analgesic use. Fentanyl has the added benefit of producing mild sedation. This study evaluated the pharmacokinetics of fentanyl patches in sheep in an effort to maximise pre and post-surgical analgesia.


A. Melnyk T. Wen J. Chak A. Kelly P. Cripton C. Fisher M. Dvorak T. Oxland

Summary Statement

Spinal flexibility in bending and axial torque has been shown to exhibit very modest changes with advancing disc degeneration. This study is the first to address the possible relationship in pure anterior shear and no clear relationship was observed.

Introduction

Disc degeneration (DD) is a risk factor for low back pain. Stable or unstable spine segments may be treated with an isolated decompression or instrumented stabilization, respectively. The effect of DD on spinal flexibility has been addressed by several groups in bending but not in shear; a highly relevant load direction in the lumbar spine is anterior shear. The objective of our study was to determine the effect of DD on anterior translation and specimen stiffness under shear loading in an in vitro model of degenerative spondylolisthesis.


M. Ferenc Ivicsics N.E. Bishop K. Püschel J.-P. Berteau M.M. Morlock G. Huber

Summary

Nucleotomy almost doubles the transmitted forces on the facet joints in human lumbar spine, regardless of the amount of removed nucleus pulposus.

Introduction

Low back pain involves the lumbar facet joints in 15% to 45% of the cases. The surgical intervention, nucleotomy, might also lead to painful facets with a high risk; however, its mechanism is yet to be fully understood. The aim of this study is to reveal how a small amount of nucleus removal can change the force transmission on the facets.


Full Access
G. Huber K. Nagel D. M. Skrzypiec A. Klein K. Püschel M. M. Morlock

Summary

Lumbar spinal specimens exhibited high fatigue strength. The cycles to failure are not only dependent on the maximum peak load, but also on the load offset or the amplitude, respectably.

Introduction

Spinal injury might be caused by whole body vibrations. The permitted exposure to vibration in the workplace is therefore limited. However, there is a lack in knowledge how external vibrations might cause internal damages. Numerical whole body models might provide the potential to estimate the dynamic spinal loading during different daily activities, but depends on knowledge about the corresponding fatigue strength. This study is aiming to determine the in vitro fatigue strength of spinal specimens from donors of working age.


J. Costi K. Heinze I. Lawless R. Stanley B. Freeman

Summary Statement

Repetitive loading of degenerated human intervertebral discs in combined axial compression, flexion and axial rotation, typical of manual handling lifing activities, causes: an increase in intradiscal maximum shear strains, circumferential annular tears and nuclear seperation from the endplate.

Introduction

Chronic low back pain (LBP) is a crippling condition that affects quality of life and is a significant burden to the health care system and the workforce. The mechanisms of LBP are poorly understood, however it is well known that loss of intervertebral disc (disc) height due to degeneration is a common cause of chronic low back and referred pain. Gross disc injury such as herniation can be caused by sudden overload or by damage accumulation via repetitive loading, which is a cause of acute LBP and an accelerant of disc degeneration. The aim of this study was to determine for the first time the relationship between combined repetitive compression, flexion and axial rotation motion of degenerated cadaver lumbar spine segments, and the progression of three-dimensional (3D) internal disc strains that may lead to disc herniation and macroscopic tissue damage.


A. Blair-Pattison J. Henke G. Penny R. Hu G. Swamy C. Anglin

Summary Statement

Incorrect pedicle screw placement can lead to neurological complications. Practice outside the operating room on realistic bone models, with force feedback, could improve safety. Pedicle forces in cadaveric specimens are reported, to support development of a training tool for residents.

Introduction

Inserting screws into the vertebral pedicles is a challenging step in spinal fusion and scoliosis surgeries. Errors in placement can lead to neurological complications and poor mechanical fixation. The more experienced the surgeon, the better the accuracy of the screw placement. A physical training system would provide orthopaedic residents with the feel of performing pedicle cannulation before operating on a patient. The proposed system consists of realistic bone models mimicking the geometry and material properties of typical patients, coupled with a force feedback probe. The purpose of the present study was to determine the forces encountered during pedicle probing to aid in the development of this training system.


R. Kueny Fl. Fensky K. Sellenschloh K. Püschel J. Rueger W. Lehmann N. Hansen-Algenstaedt M. Morlock G. Huber

Summary Statement

From a mechanical point of view, the clinical use of pedicle screws in the atlas is a promising alternative to lateral mass screws due to an increased biomechanical fixation.

Introduction

The most established surgical technique for posterior screw fixation in the atlas (C1) is realised by screw placement through the lateral mass [1]. This surgical placement may lead to extended bleeding from the paravertebral venous plexus as well as a violation of the axis (C2) nerve roots [1]. Using pedicle screws is an emerging technique which utilises the canal passing through the posterior arch enabling the use of longer screws with a greater contact area while avoiding the venous plexus and axis nerve roots. The aim of this ex vivo study was to investigate if pedicle screws in C1 bear the potential to replace the more common lateral mass screws. Therefore, the comparative biomechanical fixation strengths in terms of cycles to failure, stiffness, and removal torque were investigated.


H. Lu J. Hu Y. Cao T. Wu D. Li M. Cao

Summary Statement

In this study, we employed a novel imaging modalities, the synchrotron radiation microcomputed tomography (SRμCT) to visualise the 3D morphology of the spinal cord microvasculature and successfully obtained the 3D images.

Introduction

Understanding the morphology of the spinal cord microvasculature in three-dimensions (3D) is limited by the lack of an effective high-resolution imaging technique. In this study, we used two novel imaging modalities, conventional x-ray microcomputed tomography (CμCT) and synchrotron radiation microcomputed tomography (SRμCT), to visualise the 3D morphology of the spinal cord microvasculature and to compare their utility in basic science research.


T.M. Grupp K. Kabir B. Fritz J. Schwiesau W. Bloemer V. Jansson

Summary Statement

To evaluate carbon-fiber-reinforced PEEK as alternative biomaterial for total disc arthroplasty a closed loop between biotribology (in vitro), application of sterile particle suspensions in the epidural space of rabbits and biological response in vivo was established.

Introduction

To prevent adjacent level degeneration in the cervical spine, total disc arthroplasty (TDA-C) remains an interesting surgical procedure for degenerative disc disease. Short- or midterm complications are migration, impaired post-operative neurological assessment due to artefacts in x-ray and MRI diagnosis and substantial rates of heterotopic ossification. The idea was to create a TDA-C design based on a polymer-on-polymer articulation to overcome these limitations of the clinically established metal-on-polyethylene designs. The objective of our study was to characterise the biotribological behaviour of an experimental cervical disc replacement made out of carbon-fiber-reinforced (CFR) PEEK and evaluate the biological response of particulate wear debris in the epidural space in vivo.


O. Emohare D. Christensen R. Morgan

Summary Statement

Pedicle screws provide robust fixation and rigid immobilization. There has been no attempt to correlate the anatomic dimensions of thoracic and lumbar pedicles with the accuracy of navigated insertion. This study demonstrates that comparable accuracy using this technique.

Introduction

Pedicle screws provide robust mechanical fixation, which makes their use attractive; their use enables fixation of the three spinal columns. There remains concern about the potential both for misplacement; various investigators have studied the accuracy of pedicle screw insertions, comparing different techniques. What is not clear, however, is whether there is any relation between the variables of pedicles’ anatomic dimensions, screw dimensions and accuracy. This study aims to elucidate the relationship between these variables.


S.E.L. Detiger R.M. Holewijn R.J.W. Hoogendoorn M.N. Helder F. Berger J.P.A. Kuijer T.H. Smit

Summary Statement

Conventional imaging techniques lack the ability to objectively assess early stages of intervertebral disc degeneration, characterised by glycosaminoglycan loss. This study shows that MRI T2∗ mapping correlates positively with GAG content and that it provides continuous measurements for disc degeneration.

Introduction

Early degenerative changes arise in the nucleus pulposus (NP) and are characterised by a loss of glycosaminoglycans (GAG). Early disc degeneration (DD) could possibly be treated with upcoming regenerative therapies (e.g. with stem cells and/or growth factors). In order to evaluate degeneration and treatments, a sensitive diagnostic tool is needed. While conventional magnetic resonance imaging (MRI) and x-ray techniques can detect late stages of DD, these techniques lack the ability to detect early degenerative changes. Recently, T2∗ mapping has been proposed as a new technique to evaluate early IVD degeneration, yet the correlation with GAG content and histological features has not been previously investigated. The objective of this study was to determine the value of T2∗ mapping in diagnosing DD by correlating this technique with the biochemical composition of IVDs.


H. Arima M. Hanada T. Hayasaka N. Masaki T. Hasegawa D. Togawa Y. Yamato S. Kobayashi M. Seto Y. Matsuyama

Summary Statement

In this study, we observed that MR16-1, an interleukin-6 inhibitor, recovered phosphatidylcholine containing docosahexaenoic acid at the injury site after spinal cord injury in mice model by using imaging mass spectrometry.

Introduction

The current drugs for improving motor function of the limbs lost due to spinal cord injury (SCI) are ineffective. Development of new drugs for spinal cord injury is desired. MR16-1, an interleukin-6 inhibitor, is found to be effective in improving motor function after spinal cord injury in mice model. Thus, we examined the molecular mechanism in more detail. Therefore, the purpose of this study was to analyze the molecular changes in the spinal cord of the SCI mice treated with MR16-1 using imaging mass spectrometry.


L. Solomon S. Callary A. Mitra A. Pohl

Summary

Application of RSA in supine and standing positions allows pelvic fracture stability to be measured more accurately than current techniques. RSA may enable a better understanding of these injuries.

Introduction

The in vivo stability of the pelvic ring after fracture stabilisation remains unknown. Plain radiographs have a low accuracy in diagnosing loss of fracture reduction over time. Radiostereometric analysis (RSA) is an accurate imaging measurement method that has previously been applied to measure the healing of other fractures. This pilot study investigated the potential application of RSA in supine and standing positions to measure pelvic fracture stability over time and under weightbearing load.


J. Schilcher O. Sandberg H. Isaksson P. Aspenberg

Summary Statement

Atypical femoral fractures consist of a thin fracture line extending through the lateral cortex. The adjacent bone is undergoing resorption and mechanical abrasion and is often replaced with woven bone. The mechanical environment seems to inhibit healing.

Background

The pathophysiology behind bisphosphonate-associated atypical femoral fractures remains unclear. Histological findings at the fracture site itself might provide important clues. So far only one case describing the histological appearance of the fracture has been published.


R. Nicolescu E. Ouellette C. Kam P. Sawardeker P. Clifford L. Latta

Summary

When a TFCC tear is diagnosed, practitioners should maintain a high level of suspicion for the presence of a concomitant SL or LT ligament tear.

Introduction

Disruption of the scapholunate (SL) or lunotriquetral (LT) ligament leads to dorsal and volar intercalated segment instability, respectively, while triangular fibrocartilage complex (TFCC) tears result in distal radioulnar joint (DRUJ) instability. Viegas et al. (1993) demonstrated that 56% of grossly visualised cadaveric wrists had one or more tears of a ligament or of the TFCC. The purpose of this investigation is to quantify the incidence, distribution, and correlation of SL, LT, and TFCC tears in a large group of cadaver wrists using magnetic resonance imaging (MRI). Additionally, statistical analysis was performed to predict.


R. Nicolescu E. Ouellette P. Clifford C. Kam P. Sawardeker L. Latta

Summary

Practitioners should maintain a high suspicion of concurrent carpal fractures in patients who present with a distal radius fracture after a fall onto an outstretched hand, particularly if forearm rotation is involved.

Introduction

Simultaneous scaphoid and distal radius fractures, and the importance of their identification, have been previously described in multiple reports. However, few studies have investigated the incidence of carpal fractures, in general, occurring concurrently with distal radius fractures after a common mechanism of wrist injury. The purpose of this study is to investigate the incidence and characteristics of carpal fractures occurring simultaneously with distal radius fractures after a fall onto an outstretched hand. We hope to determine whether different fall parameters, such as hand position and forearm rotation, influence the frequency of this injury.


H.-L. Lu C.-C. Kuo C.-C. Lin T.-W. Lu

Summary Statement

The current study introduced the effects of projection errors on ankle morphological measurements using CT-based simulated radiographs by correlation analysis between 2D/3D dimensions and reliability analysis with randomised perturbations while measuring planar parameters on radiographs.

Introduction

Clinical success of total ankle arthroplasty (TAA) depends heavily on the available anatomy-based information of the morphology for using implants of precisely matched sizes. Among the clinically available medical imaging modalities, bi-planar projective radiographs are commonly used for this purpose owing to their convenience, low cost, and low radiation dose compared with other modalities such as MRI or CT. However, the intrinsic articular surface of the ankle joint is not symmetrical and oblique which implies that it is difficult to describe all the anatomical dimensions in detail with only one radiograph, thereby hindering the determination of accurate ankle morphometric parameters. The purposes of this study were to compare the measurements of ankle morphology using 3D CT images with those on planar 2D images; and to quantify the repeatability of the 2D measurements under simulated random perturbations.


E. Ouellette W. Elliott L. Latta E. Milne D. Kaimrajh J. Lowe A.-L. Makowski E. Herndon C. Kam P. Sawardeker

Summary

For injuries to the lower leg or forearm, supplemental support from soft tissue compression (STC) with a splint or brace-like system and combined with external fixation could be done effectively and quickly with a minimal of facilities in the field.

Introduction

Soft tissue compression (STC) in functional braces has been shown to provide rigidity and stability for most closed fractures, selected open fractures and can supplement some other forms of fracture fixation. However, soft tissue injuries are compromised in war injuries. This study was designed to evaluate if STC can provide adequate rigidity and stability either with, or without other forms of fixation techniques of simple fractures or bone defects after standardised soft tissue defects. The load was applied either axially or in bending as the bending configuration is more like conditions when positioned on a stretcher in the field.


M.T. Ovaska T.J. Mäkinen R. Madanat V. Kiljunen J. Lindahl

Summary

Syndesmotic malreduction or failure to restore fibular length are the leading causes for early reoperation after ankle fracture surgery. Anatomic fracture reduction and congruent ankle mortise can be achieved in the majority of cases following revision surgery.

Introduction

The goal of ankle fracture surgery is to restore anatomical congruity. However, anatomic reduction is not always achieved, and residual talar displacement and postoperative malreduction predispose a patient to post-traumatic arthritis and poor functional outcomes. The present study aimed to determine the most common surgical errors resulting in early reoperation following ankle fracture surgery.


V. Moretti B. Goldberg

Summary Statement

Total hip arthroplasty and hemi-arthroplasty are becoming increasingly popular in the treatment of femoral neck fractures in the United States. Both appear to be safe and effective treatment options, with rare acute adverse events and low mortality.

Introduction

Femoral neck fractures are one of the most frequent orthopaedic injuries seen in the United States (US). Total hip arthroplasty (THA) and hemiarthroplasty (HA) are commonly used to treat displaced intra-capsular femoral neck fractures, but controversy currently exists regarding the preferred modality. The purpose of this study was to assess recent national trends in THA and HA performed for femoral neck fracture and to evaluate perioperative outcomes for each treatment group.


O. Sandberg B. Macias P. Aspenberg

Summary

These data suggest that PTH treatment for stimulation of bone healing after trauma is not much dependent on mechanical stimulation and therefore, roughly equal treatment effects might be expected in the upper and lower extremities in humans.

Introduction

Stimulation of bone formation by PTH is known to, in part, act via increased mechanosensitivity. Therefore, unloading should decrease the response to PTH treatment in uninjured bone. This has served as a background for speculations that PTH might be less efficacious for human fracture treatment in unloaded limbs, e.g. for distal radial fractures. We analyzed if the connection with mechanical stimulation also pertains to bone formation after trauma in cancellous bone.


O. Sandberg P. Aspenberg

Summary

The negative impact of NSAIDs on fracture healing appears not to pertain to fractures in cancellous bone. Possibly this is because of a higher prevalence of MSCs in cancellous bone, making recruitment of distant cells via inflammatory signals less important.

Introduction

It is well established that cox inhibitors (NSAIDs) impair fracture healing, also in humans. However, as they provide good pain relief it is unclear when to avoid these drugs. The healing process in cortical and cancellous fractures differs regarding progenitor cell sources, and inflammation might be involved in the recruitment of cells from distant sources. We therefore hypothesised that fractures in cancellous bone are less sensitive to reduced inflammation due to cox inhibitors.


K. Wang Gang Li

Summary Statement

Umbilical cord derived stem cell secretion could enhance the osteogenic differentiation of human bone marrow stem cells. It may promote bone, cartilage and tendon regeneration in rat models, but the effect was not significant up to now.

Introduction

Mesenchymal stem cells (MSCs) are multipotent cells that have extensive proliferative capacity. MSCs synthesise various exosomes, growth factors and cytokines. Stem cell secretions were made from serum free conditioned medium of stem cells collected from different human tissues, such as adipose tissue and dental pulp. Our hypothesis is umbilical cord stem cell secretion could promote multiple proliferation and differentiation of MSCs, also enhance the regeneration of musculoskeletal tissues.


M. Deschepper J. Paquet M. Manassero D. Logeart-Avramoglou M. Bensidhoum H. Petite

Summary

In this study, we challenged the current paradigm of human Mesenchymal Stem Cells survival, which assigned a pivotal role to oxygen, by testing the hypothesis that exogenous glucose may be key to their survival.

Introduction

The survival of human mesenchymal stem cells (hMSCs) has elicited a great deal of interest, because it is relevant to the efficacy of engineered tissues. However, to date, hMSCs have not met this promise, in part due to the high death rate of cells upon transplantation. In this study, we challenged the current paradigm of hMSC survival, which assigned a pivotal role to oxygen, by testing the hypothesis that exogenous glucose may be key to hMSC survival.


N. Kohli M. Snow E. Johnson

Summary

The findings demonstrate that culture expanded human mesenchymal stem cells (MSCs) incorporated and proliferated in clinically relevant cell scaffolds better than freshly isolated bone marrow mononucleated cells (MNCs); in fact, only in MSC cultures were cells present for longer term chondrogenic inductions.

Introduction

The treatment of chondral defects poses a significant clinical problem and a variety of cell sources and techniques have been studied and practiced to regenerate cartilage. Preclinical and clinical evidence suggests that MSCs can help regenerate cartilage when transplanted into cartilage lesions. However, the uptake of MSCs for cell therapies is limited due to the need for their culture expansion to generate subsequent numbers for transplantation. An alternative is to use minimally manipulated MNCs, which avoids the costs and regulatory implications of culture expansion and would enable the treatment of cartilage defects in a one-step procedure. Therefore, this study has focused on comparing these two cell types within three different scaffolds that can currently be used as cell delivery systems.


A. Bhattacharjee J.H. Kuiper P.E. Harrison S. Roberts J.B. Richardson

Summary

Randomised controlled study evaluating new bone formation in vivo in fracture non-unions by bone marrow derived stromal cells (BMSC). These cells do not show statistically significant new bone formation. Age of the patient during fracture, diabetes and doubling time had been observed to be correlated with fracture healing.

Introduction

Regenerating new bone by cell therapy could provide therapeutic options in many conditions such as fracture non-unions and osteo-chondral defect regeneration in advance OA. In this randomised controlled study we evaluated the efficacy of new bone formation by bone marrow derived stromal cells (BMSC) in patients with non-union.


H. McCarthy C. Archer

Summary Statement

Extended expansion of cells derived from equine articular cartilage reveal maintenance of chondrogenic potency and no evidence of senescence up to 100 population doublings. The data suggests the reclassification of these cells from progenitor cells to stem cells.

Introduction

One sign of ‘in vitro aging’ is the diminishing capacity for cell division. In contrast to embryonic stem cells that show no loss of proliferative potency, the maximal population doublings (PD) for mesenchymal stem cells (MSCs) in vitro is reported to be between 30 and 40 replications 1,2,3. We have isolated a population of chondroprogenitor cells from articular cartilage of several species, including equine4.

These cells have demonstrated functional equivalence in their differentiation capacity when compared with MSCs but have the advantage of retaining the highly desirable stable (permanent) chondrocyte phenotype. In this study, we examined the age-related capacity of these cells for extended division and retention of potency.


A. Govil N. Thompson

Summary

The BMP-2 content and bone forming potential of 2 leading allograft products (OsteoAMP® and Osteocel® Plus) was tested across 3 commercially available lots. Surprisingly, there was no BMP-2 content associated with the cells contained within Osteocel® Plus. OsteoAMP® contained greater than 1000 times the overall BMP-2 content than Osteocel® Plus. Correspondingly, Osteocel® Plus did not form new bone at any timepoint in the 12 week in vivo study while OsteoAMP® had increasing new bone formation at each sequential timepoint. Interestingly, the highest cellularity of Osteocel® Plus was just prior to implant at t0, decreasing at each timepoint, decreasing further at the terminal endpoint of the study at 12 weeks (82% of cells had died or migrated). Conversely, the cellularity of OsteoAMP® increased at each timepoint.

Introduction

Implants containing living cells are often characterised by the orthobiologics industry as ‘osteogenic’. The positive function and ultimate fate of these cells has been assumed with little to no proof of efficacy. In this study we compare the bone forming ability of the market leading stem cell product claiming osteoinductivity as well as osteogenicity, Osteocel® Plus, against the market leading allograft derived growth factor product, OsteoAMP® which claims osteoinductivity but contains no viable cells. The goal of the study is to determine if a cellular product will form new bone or produce a false positive when evaluated histomorphometrically using an osteoinductive control over time in vivo. Additionally, the osteoinductive potential from each product will be quantified by in vitro by measurement of BMP-2 content via ELISA.


A. Decambron M. Manassero M. Bensidhoum H. Petite V. Viateau

Summary

MSCs could promote bone regeneration in sheep when loaded on natural fully-resorbable scaffolds, but results are highly variable. Improving the ultimate performance of cell-containing constructs cannot be limited to the decreased rate of scaffold resorption.

Introduction. Tissue constructs containing mesenchymal stem cells (MSCs) are an appealing strategy for repairing massive segmental bone defects. However, their therapeutic effectiveness does not match that of autologous bone grafts; among the failure reasons the scaffold resorbability has been identified as a critical feature for achieving bone regeneration. In the present study, the osteogenic potential of 2 constructs obtained by expanding in a bioreactor autologous MSCs onto granules of Acropora or Porites coral, natural fully-resorbable scaffolds, was compared.

Materials and methods

15 sheep underwent a 25 mm long metatarsal ostectomy stabilised with a 3.5 DCP plate. Bone defects were replaced with (i) MSCs-Acropora constructs (n=7), (ii) MSCs-Porites constructs (n=6), (iii) autograft (n=2). Animals were sacrificed 4 months later and bone healing and coral resorption was documented by radiographic, histologic and microCT studies.


P.D. Parchi M. Cecchini S. Antonini N. Piolanti L. Andreani A. Poggetti M. Lisanti V. Orazio

Summary

Aim of this study is to design, develop and preclinical test PET nanostructured scaffolds for the transplantation and differentiation of MSCs in the treatment of bone defects. The interaction of cells with nanotopographical features has proven to be an important signaling modality in controlling MSC differentiation.

Introduction

The wide bone defects, caused by trauma, tumor, infectious, periprosthetic osteolysis, need to be surgically treated because their low potential of repair. Nowadays the bone allograft and autograft represent 80% of all transplantation done in the world. However this technique shows many disadvantages, such as the risk of infections, the immunological rejection, the low bone availability and the high costs. These reasons have motivated extensive research to find alternative strategies. As shown in literature, the future strategies are based on the synergic combination of different methodologies: use of biomimetic scaffold in order to support bone regeneration, use of mesenchymal stromal cells (MSCs) and growth factors. Successful regeneration necessitates the development of tissue-inducing scaffolds that mimic the hierarchical architecture of native tissue extracellular matrix (ECM). Cells in nature recognise and interact with the surface topography they are exposed to via ECM proteins. Here we are going to show the guidelines recently published for the design and development of nanostructured scaffolds for the bone regeneration, and the morphofunctional changing of MSCs interacting with nanogratings.


L. Obert F. Gindraux P. Garbuio

Introduction

20 cases of bone defect have been treated by the induced membrane technique avoiding allograft, microsurgery and amputation

Material and Methods

9 cases of long bone defect (humerus and 2 bones arm) and 11 cases of bone defct at the hand have been included in this multicentric prospective study (3 centers). 11 cases were traumatic, 7 cases were septic non union and 2 cases were tumor. At hand level's bone reached at least one phalanx, and for long bone the mean defect was 5cm (3–11). All cases were treated by the induced membrane technique which consists in stable fixation, flap if necessary and in filling the void created by the bone defect by a cement spacer (PMMA). This technique needs a second stage procedure at the 2nd month where the cement is removed and the void is filled by cancellous bone. The key point of this induced membrane technique is to respect the foreign body membane which appeared around the cement spacer and which create a biologic chamber after the second time. Bone union was evaluated prospectively in each case by an surgeon not involved in the treatment by Xray and CT scan. Failure was defined as a non union at 1 year, or an uncontrolled sepsis at 1 month.


X. Han W. Gao L. Chen H. Yang Q. Shi

Summary

Collagen scaffolds loaded with mesenchymal stem cells accelerate neurological recovery in rat spinal hemisection.

Objective

To investigate the implantation effects of the collagen scaffold (CS) combined with mesenchymal stem cells (MSCs) on the function recovery of spinal cord injury (SCI) with a lateral hemisection SCI SD rat model.


O. Charyeva U. Thormann S. Schmidt U. Sommer K. Lips L. Heimann R. Schnettler

Summary Statement

Magnesium has a number of qualities suitable for bioresorbable metallic implants. However, high corrosion rate and formation of hydrogen gas can compromise its performance. Combining magnesium with calcium phosphate improves magnesium's biocompatibility by decreasing gas formation and increasing bone remodeling.

Introduction

Clinical problems like risk of postoperative infection and increased incidence of pediatric trauma requiring surgical intervention raised the need for temporary orthopedic implants that would resorb after the bone healing is complete. This would decrease high costs associated with repeated surgeries, minimise recovery times, decrease the risk of postoperative infections, and thus promote higher quality of life to the patients. The specific requirement for orthopedic implants, aside from being bioresorbable, is the ability to bear high loads. Magnesium was suggested as a suitable material for these purposes because it is biocompatible; has excellent mechanical properties; is natural for human body, and seems to stimulate new bone formation. However, an important problem with magnesium is high corrosion rate with consistent hydrogen gas formation on contact with fluids. This in vivo study focuses on investigation of new magnesium-based implants specifically designed to minimise hydrogen gas formation.


O. Hakimi P.-Al. Mouthuy C. Yapp A. Wali N. Zargar Baboldashti A. Carr

Summary Statement

The aim of this study was to compare patterns (aligned, random and grid) of electrospun polydioxanone scaffolds for tendon repair. The aligned design was optimal, directing cell shape, orientation and protein expression. Moreover, it naturally crimped, presenting tendon-like morphology.

Introduction

Nanofibrous electrospun materials have been previously proposed as potential scaffolds for tendon repair, with emphasis on biomimetic design, postulated to encourage tissue regeneration. In this study, we characterised the interaction of primary tendon-derived cells with polydioxanone (PDO) scaffolds. PDO is a polymer with an excellent in vitro and in vivo biocompatibility, and is specifically compatible with tendon-derived cells. Here, we designed electrospun PDO scaffolds with different fibre orientations, namely aligned, random and grid-like patterns. To evaluate their potential as patches for tendon repair, we grew primary tendon derived cells on these scaffolds, and tested different aspects of cell behavior, including cell shape, proliferation and protein expression.


D. Bociaga P. Niedzielski J. Grabarczyk D. Nowak B. Walkowiak

Summary Statement

Innovative nanocomposite carbon coating doped with Si can significantly improve the osseintegration of orthopaedics implants. Additionally, this kind of coating increases the mechanical resistance of the implants, what is especially important on case of joints (frictional pairs).

Introduction

Use of layers of carbon-doped silicon, which leads to the synthesis of layers improving mechanical and biological characteristics, let obtain good strength by volume features. Suitable introduction to the structure of amorphous silicon dioxide layer allow for the production of higher adhesion to metallic substrates and consequently the increased thickness and hardness. The increased thickness of the layer leads to a stronger diffusion barrier to harmful metal ions from the implant material and thus consequently improving the biocompatibility of the implant. Moreover, a silicon beneficial effect on stress relaxation layer formed during the synthesis. This allows for improved biocompatibility, also affects other property obtained in the case of silicon carbide layers, the bacteriastability. This further protects the surface of the implant against the risk of bacterial colonization in both the implantation and subsequent use in the body, and preferably suppressing inflammation and faster healing of surgical wounds. The thus obtained product is much better than the biological and mechanical parameters of currently offered.


J. Liskova O. Babchenko M. Varga A. Kromka D. Hadraba Z. Svindrych Z. Burdikova L. Bacakova

Summary Statement

O-terminated nanocrystalline diamond films proposed as bone implant coatings are promising for adhesion and growth of osteoblasts, as well as for osteogenic cell differentiation and extracellular matrix production.

Nanocrystalline diamond (NCD) films are promising materials for tissue engineering, especially for bone implants coating, due to their biocompatibility, chemical resistance and mechanical hardness. Nanostructure and morphology of the NCD films can efficiently mimic the properties of natural tissues, and thus they support the cell adhesion, proliferation and differentiation. In addition, the NCD wettability can be tailored by grafting specific atoms and functional chemical groups (e.g., oxygen, hydrogen, amine groups, etc.) which influence the adsorption and final geometry of proteins, and thus the behaviour of cultivated cells. Therefore, the NCD films are proposed as multifunctional materials for fundamental studies on the growth and adhesion of osteoblasts on bone implants, which is particularly our interest.

The NCD films used in this study were grown on silicon substrates by microwave plasma-enhanced chemical vapor deposition. The quality of the grown NCD films was investigated by Raman spectroscopy, scanning electron microscopy and atomic force microscopy. In order to control the hydrophobic or hydrophilic character, the NCD film surfaces were grafted by hydrogen (H-termination) or oxygen (O-termination) atoms. The influence of surface termination on the surface wettability (wetting contact angle) was characterised by reflection goniometry using droplet of deionised water. The primary human osteoblasts and osteoblast-like Saos-2 cells were used for biological studies on H- and O-terminated NCD films. The cell adhesion and spreading was analysed by the visualisation of focal adhesion proteins (talin, paxillin) and actin fibers. Expression of markers of osteogenic cell differentiation (alkaline phosphatase, osteocalcin, collagen I) was monitored by the reverse transcription and Real-time PCR method, and also by immunostaining of expressed proteins and image analysis. The extracellular matrix production and composition, i.e. collagen content, calcium content and activity of alkaline phosphatase, were also quantified. Native type I collagen fibres were visualised by two-photon excitation microscopy and second harmonic generation imaging, together with immunostaining and fluorescence microscopy.

We found that primary human osteoblasts cultivated on the O-terminated NCD films exhibited better adhesion compared to the H-terminated NCD films. Also the expression of osteogenic cell markers such as collagen and osteocalcin was higher on the O-terminated films. The mature collagen fibers were detected in Saos-2 cells on both H- and O-terminated NCD films; however, the quantity of collagen in extracellular matrix was higher on O-terminated NCD films. The amount of calcium and alkaline phosphatase activity were also significantly higher in Saos-2 cell layers on O-terminated NCD films. In conclusion, the higher wettability of the O-terminated NCD films (contact angle < 20°) is promising for adhesion and growth of osteoblasts. Besides, the O-terminated surface also seems to support the osteogenic differentiation of the cultivated cells, production of extracellular matrix proteins and subsequent extracellular matrix mineralization.

This work was supported within the project “The Centre of Biomedical Research” (CZ.1.07/2.3.00/30.0025). This project is co-funded by the European Social Fund and the state budget of the Czech Republic. Other supports were provided by the Grant Agency of the Czech Republic (grant No. P108/11/0794).


N. Emanuel Y. Rosenfeld O. Cohen R. Estrada Y. Applbaum Y. Barenholz R. Gustilo S. David

Bacterial infection of bone may result in bone destruction which is difficult to cure due to poor accessibility to bone of systemically-administrated antibiotic and poor performance of currently available local antibacterial treatments. PolyPid Ltd developed a novel local drug delivery system based on self-assembly of pharmaceutically approved lipids and polymers that encapsulate doxycycline (Doxy). The formulation is self-assembled lipid matrix via the interaction of the lipids (cholesterol and synthetic phospholipids) and biocompatible - biodegradable polymer (poly-lactic-co-glycolic).

The entrapped Doxy is located within the anhydrous environment and therefore fully protected from both enzymatic and long-term water-exposure-related degradation. The fine coating of the tri-calcium phosphate (TCP) bone filler by this Doxy-containing formulation (BonyPid™) is capable of releasing intact and active drug at zero-order kinetics for a predetermined period of up to 30 days. The coating of the TCP granules with the polymer-lipids-Doxy formula (BonyPid™) did not change the granules’ macroscopic shape, but altered its color from white to pale yellow, which resemble the color of the entrapped Doxy. The average sizes of the non-coated TCP granules and the coated granules BonyPid™ were similar, as determined by measuring the widest dimension of each granule (1135±241 µm and 1072±242 µm, respectively, P=0.16). The MIC for Doxy that was released from BonyPid™ at different time points was similar to the non-encapsulated Doxy, suggesting full bioavailability of the released drug. BonyPid™ formulation structure was characterised by different physical methods including wide angle X-ray analyses (WAXS), differential scanning calorimetric (DSC) and SEM. WAXS analyses of BonyPid™ samples show a strong signal in the range of 1.3–1.8 2θ°, suggesting that the polymer and lipid TCP coating is a highly organised nano-substructure.

The principle lipid in BonyPid™ formulation is phosphatidylcholine, which constitutes more than 85% of the overall lipid mass. It was found that the length of the acyl chains (14, 16 and 18 carbons, respectively) can significantly alter the release rate of Doxy during the prolonged (30 days), zero-order release phase, but did not alter the release profile. The anti-infection activity of BonyPid™ was tested in the rabbit tibia model contaminated with 5×105S. aureus. Both acute and chronic infection models were tested. Only BonyPid™ treatment demonstrated a statistically significant reduced bone absorption over the infected group (P<0.04 for day 7, 14 and 21) and significantly lower bacterial bone concentration (p>0.05) on day 21 following the bone grafting and the bacterial inoculation. In addition it was found that BonyPid™ did not reduce the osteo-conductivity as compared to non-coated TCP bone-filler. The first-in-man study for the treatment of contaminated / infected severe open long-bone fractures of BonyPid™ completed its 6 months follow-up. The results demonstrated high safety profile and significant efficacy; early bone callus formation and 0% infections in the BonyPid™ target bone fracture.

Conclusion

Results demonstrate that BonyPid™ nan-technology that allow one month release of doxycycline in a controlled manner provides a new way for treating open fractures. This new local antibiotic delivery system is applicable in other medical situations associated with localised infections.


P.-A. Mouthuy O. Hakimi N. Zargar Baboldashti M. Morrey E. Lostis A. Carr

Summary Statement

This study describes the design and preliminary in vitro testing of a novel patch for the repair of rotator cuff tendon tears. The laminated design incorporates woven and electrospun components. The woven element provides the patch with excellent mechanical strength and the electrospun layer improves cell attachment and promotes cell orientation and diferentiation.

Introduction

Aligned nanofibrous electrospun scaffolds have been previously proposed as ideal scaffolds for tendon repair, replicating the anisotropy of tendon and providing a biomimetic design to encourage tissue regeneration (Hakimi et al., 2012). However, such scaffolds are still limited in terms of mechanical properties. This paper presents the design of a novel patch for rotator cuff repair in which the electrospun scaffold is supported by a woven component.


V. Melli G. Rondelli E. Sandrini L. Altomare G. Bolelli B. Bonferroni L. Lusvarghi R. Chiesa L. De Nardo

Summary

Metal Injection Molding could provide cost saving of about 20–50% for implantable medical device manufacturing and hence healthcare public spending. Corrosion behaviour and biocompatibility of the new manufactured alloy were studied and showed similar behaviour compared to the traditional one.

Introduction

The growing trend for total joint arthroplasties could raise healthcare costs in the near future. Metal Injection Molding (MIM) is a near net shape manufacturing technology and allows the production of finite prosthesis components saving the machining step, and so resources, up to 20–50%. In order to apply such process to the production of actual devices, the bulk material have to show biocompatibility and corrosion behaviour similar to the traditional one. (ASTM F2083, ISO 21536) The aim of this work was to compare cast and forged CoCrMo alloy with the MIM one from the electrochemical point of view and cytocompatibility.


M. Pettersson C. Skjöldebrand H. Engqvist C. Persson

Summary Statement

The chemistry, amount, morphology, and size distribution of wear debris from silicon nitride coatings generated in the bearing surface can potentially reduce the negative biological response and increase the longevity compared to conventional materials in joint replacements.

Introduction

Total hip implants have a high success rate at 15 years of implantation, but few survive over 25 years. At present, revisions are mostly due to aseptic loosening, believed to mainly be caused by the biological response to wear debris generated in the joint bearing. For the polymer liners the size of the wear debris determines the biological response, while for metal bearing surfaces a limitation is the metal ion release. When ceramics are used, the wear debris is in general small and mechanical factors may be the main cause for failure. A more recent, experimental alternative is to let the well-known metallic substrate serve as the soft, tough bulk, and additionally apply a hard and smooth ceramic coating. In this way a lower wear rate and reduced metal ion release could be obtained. Furthermore, the chosen composition, silicon nitride (SixNy), contains no detrimental ions, and silicon nitride debris has been shown to slowly dissolve in aqueous medium. Altogether, it can potentially increase the longevity of the implant. However, the debris from SixNy coatings has not yet been characterised. In this study, a wear model test was performed to generate wear debris from SixNy coatings. The debris was characterised using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) in combination with computational calculations.


D. Bichara E. Malchau N. Sillesen S. Cakmak O. Muratoglu

Summary Statement

Vitamin E-UHMWPE particles have a reduced osteolysis potential in vivo when compared to virgin, highly cross-linked UHMWPE in a murine calvarial bone model.

Introduction

Ultra high-molecular weight polyethylene (UHMWPE) particle-induced osteolysis is one of the major causes of arthroplasty revisions. The lack of particle clearance from the joint inevitably leads to the upregulation of the inflammatory cascade, resulting in bone resorption and implant loosening. Recent in vitro findings (Bladed CL et al. ORS 2011 and J Biomed Mater Res B Appl Biomater, 2012) have suggested that UHMWPE wear particles containing vitamin-E (VE) may have reduced functional biologic activity and decreased potential to cause osteolysis. This is of significant importance since VE-stabilised cross-linked UHMWPEs were recently introduced for clinical use, and there is no in vivo data determining the effects of wear debris from this new generation of implants. In this study we hypothesised that particles from VE-stabilised, radiation cross-linked UHMWPE (VE-UHMWPE) would cause reduced levels of osteolysis in a murine calvarial bone model when compared to virgin gamma irradiated cross-linked UHMWPE.


V. Bulgakov N. Gavryushenko A. Shal'nev

Summary

Understanding of the role of the radical-generating ability of wear particles of the existing and new implant materials as well as application of efficient antioxidants is one of the necessary conditions for improvement of the results of joint replacements.

Introduction

Functioning of joint prostheses is accompanied by a continuous formation of wear particles and their accumulation in surrounding tissues. The impact of microroughnesses of joint prosthesis friction units may bring about chemical bond breakage and free-radical generation on a newly-formed wear surface. Wear particles of orthopedic alloys are capable to produce free radicals, and Co-Cr-Mo alloy particles are especially active. Free radicals generated by wear particles can cause oxidation and reduced wear resistance of polyethylene. Oxidised polyethylene particles stimulate the activity and release of bone-resorbing cytokines by human monocytes/macrophages. The ability of free radicals to cause damage to surrounding tissues and implant components makes it necessary to estimate comprehensively the radical-generating activity of wear particles of different orthopedic materials and develop the ways of its inhibition.


Full Access
J. Shepherd G. Riley H. Screen

Summary Statement

Tendon micromechanics were investigated using 2 methods. When collagen deformation was measured directly, higher levels of inter-fibre sliding were observed than when tenocyte nuclei were tracked. This suggests that under high strain tenocytes become unattached from the collagen fibres.

Introduction

Fibre extension and inter-fibre sliding have both been reported during tendon extension, but fibre sliding is believed to be the predominant mechanism in normal healthy tendon function. Fatigue damage is known to result in structural changes and reduced mechanical properties, but its influence on micromechanics is unknown.

This work aimed:

To investigate the effect of fatigue loading on bovine digital extensor fascicle micromechanics, comparing fibre extension and fibre sliding, hypothesising that the relative importance of these may change due to fatigue damage.

To compare two techniques for characterising micromechanics: bleaching of a grid to directly measure collagen deformation, and using the cells as fiducial markers of fibre movement.


B. Dean E. Lostin T. Oakley M. Morrey A. Carr

Summary Statement

The effects of local glucocorticoid on tendon appear broadly negative and this supports the emerging clinical evidence which points toward significant long term harms associated with this treatment modality.

Introduction

The use of locally administered glucocorticoid is widespread in the treatment of painful tendinopathy. Despite evidence of short term benefit, the emerging evidence points toward significant long term harms associated with this method of treatment, including an increased risk of recurrence, rupture and worsened clinical outcomes (1, 2). Our primary purpose was to summarise the known effects of locally administered glucocorticoid on tendon tissue and tendon cells.


S. Durgam S. Mayandi M. Stewart

Summary

Objective assessment of tendon histomorphology, particularly in the context of tissue repair, requires comprehensive analyses of both cellular distribution and matrix architecture. Fourier Transform analyses of histological images collected with second harmonic generation (SHG-FT) technique provide objective, quantitative assessment of collagen fiber organization with high specificity. Concurrent nuclear staining allows simultaneous analyses of cell morphology and distribution.

Introduction

Tendon injuries can be career-limiting in human and equine athletes, since the architectural organization of the tissues are lost in the course of fibrotic repair. Objective assessment of tendon repair is problematical, particularly in research addressing potential therapies. Fourier Transform analyses of histological images collected with second harmonic generation (SHG-FT) technique can provide objective, quantitative assessments of collagen fiber organization with high specificity. This study describes the use of SHG-FT with fluorescently-labelled tendon-derived cells (TDC) in an in-vivo model of equine tendinitis to assess the temporal and spatial effects of cell delivery on collagen fiber organization.


J. Dudhia N.J. Werling S.G. Dakin A.E. Goodship R.K. Whealands Smith

Summary

Treatment of equine naturally occurring over-strain tendinopathy with mesenchymal stem cells suspended in bone marrow supernatant resulted in significant improvements compared to saline treated tendons in the normalisation of biomechanical, morphological, and compositional parameters with no adverse effects.

Introduction

Tendon injuries are a common age-related degenerative condition where natural repair involves scarification, resulting in a functionally inferior tissue1 that frequently re-injures. Naturally-occurring human and equine tendinopathy possess many similarities2 making the horse a good clinically-relevant model. A multitude of treatments are used but few have a strong evidence base. Regenerative approaches using mesenchymal stem cells (MSCs) to improve outcome are supported by clinical data demonstrating reduced re-injury rates in racehorses3. We therefore hypothesised that implantation of autologous MSCs into injured equine tendons would result in a tissue more closely resembling normal tendon matrix than the fibrous scar tissue formed subsequent to natural repair. The aim of this controlled experimental study was to assess the biomechanical, histological and compositional parameters following MSCs implantation into naturally injured tendons.


D. Stanco M. Viganò G. Thiebat L. de Girolamo

Summary

Mesenchymal stem cells from human semitendinosus and gracilis tendons (TSPCs) could be a promising MSCs resource for tissue-engineering application. In comparison to adipose-derived stem cells, TSPCs possess similar stem-cells properties and a higher chondrogenic differentiation potential.

Introduction

Mesenchymal stem cells (MSCs) isolated from bone marrow (BMSCs) or adipose tissue (ASCs) have been deeply characterised for their usefulness in musculoskeletal tissue regeneration. However, other potentially valuable MSCs sources have been recently proposed. The goal of this study was to isolate MSCs from human semitendinosus and gracilis tendons (TSPCs, tendon stem progenitor cells) and to compare their features with that of human ASCs.


E. Saether C. Chamberlain E. Leiferman W.-J. Li R. Vanderby

Summary Statement

This study explores the therapeutic use of MSCs to enhance ligament healing from an immuno-modulatory perspective. We report improved healing with MSC treatment, but inconsistent effects on inflammatory markers.

Introduction

Mesenchymal stem cell (MSC) use continues to hold untapped potential as a therapeutic agent because: 1) MSCs have the ability to differentiate into several different connective tissues such as cartilage, bone, muscle and fat (1–3), and 2) MSCs can modulate immune and inflammatory responses that affect healing (4, 5). This paradigm shift from differentiation to immune modulation is being studied for different applications (6). Several studies suggest MSCs decrease inflammation by reducing pro-inflammatory cytokines and changing the macrophage phenotype from M1 (classically-activated) to M2 (alternatively-activated) (7–10). However, their immune-modulatory effects within a healing ligament remain unexplored. MSCs can behave differently depending on the tissue and healing environment they encounter, which leads to our interest in MSC immune-modulation in healing ligaments.


K. Imai K. Ikoma R. Gay T. Hirano Y. Ozasa Q. Chen K.-N. An C. Zhao

Summary Statement

ASTM therapy is commonly used to treat Achilles tendinopaty. However, there was no report to evaluate the biomechanical effects, especially the dynamic viscoelasticity. We have shown that ASTM treatment was biomechanically useful for chronic Achilles tendinopathy in an animal model.

Introduction

Achilles tendinopathy is a common chronic overuse injury. Because Achilles tendon overuse injury takes place in sports and there has been a general increase in the popularity of sports activities, the number and incidence of Achilles tendon overuse injury has increased. Augmented Soft Tissue Mobilization (ASTM) therapy is a modification of traditional soft tissue mobilization and has been used to treat a variety of musculoskeletal disorders. ASTM therapy is thought to promote collagen fiber realignment and hasten tendon repair. It might also change the biomechanical behavior of the injured tendon, especially the dynamic viscoelasticity. The purpose of this study is to evaluate the effect of ASTM therapy in a rabbit model of Achilles tendinopathy by quantifying dynamic biomechanical properties and histologic features.


K.H.L. Kwan K. Yeung K. Cheung M.K.T. To

Summary

Silver nanoparticles improve the tensile property of the repaired Achilles tendon by modulating the synthesis and deposition of collagen. This makes silver nanoparticles a potential drug for tendon healing process with less undesirable side effect.

Introduction

Tendon injury is a common injury that usually takes a long time to fully recover and often lead to problems of joint stiffness and re-rupture due to tissue adhesions and scarring on the repaired tendon respectively. Recently, it has been proven that silver nanoparticles (AgNPs) are capable of regenerating skin tissue with minimal scarring and comparable tensile property to normal skin. Hence, it is hypothesised that AgNPs could also improve the healing in tendon injury as both tissues are predominating with fibroblasts. The objective of this study is to look at the in vitro response of primary tenocytes to AgNPs and to investigate the mechanical and histological outcome in vivo.


V. Shim J. Fernandez P. Gamage C. Regnery P. Hunter D. Lloyd T. Besier

Summary Statement

Subject specific FE models of human Achilles tendon were developed and optimum material properties were found. Stress concentration occurred at the midsection but dependent on stiffening and thinning of tendon, indicating that they are two major factors for tendon rupture.

Introduction

Achilles tendon injuries are common, occurring about 250,000 per year in the US alone, yet the mechanisms of tendinopathy and rupture remain unknown. Most Achilles tendon ruptures occur at 2 to 6 cm above the insertion to the calcaneus bone. Previous angiographic studies have suggested that there is an avascular area in this region. However, it is not understood why that region receives poor blood supply and prone to rupture. The aim of this study is to investigate influence of geometry and material properties on Achilles tendon rupture with mechanical experiment and corresponding subject-specific finite element (FE) analysis.


L. Zhao A. Thambyah N. Broom

Summary

The presence or absence of crimp within the anterior cruciate ligament (ACL) sub-bundle anatomy was correlated with knee flexion angle changes and provided a measure of differential loading within its sub-bundle microstructure.

Introduction

Previous studies have shown that macroscopically the anteromedial (AM) and posterolateral (PL) bundles of the ACL tighten/slacken differently with knee flexion angle. This research used fibre crimp morphology, revealed following in situ fixation of the intact ligament structures, to investigate patterns of differential fibre recruitment across each ACL sub-bundle.


Y.B. Ong C.L. Poh T.S. Howe Y.H. Ng A. Yew J.S.B. Koh B.F. Morrey

Summary Statement

This 3-dimensional CT study on cadaveric proximal ulna provides further insight into the size and geometry of the proximal ulna intramedullary cavity with potential applications to design and sizing of proximal ulna components.

Introduction

Total elbow arthroplasty (TEA) is an established treatment for varying pathologies of the elbow with very good functional outcomes. Optimal fit of ulna components in TEA is predicated on a detailed appreciation of the 3-dimensional anatomy of the proximal ulna intra-medullary cavity, but literature remains scarce. Three-dimensional (3D) models of the proximal ulna have been constructed using computed tomography (CT) programs, accurately defining the angular relations with the cross-sectional extra-medullary dimensions. However, current CT-based thresholding techniques lack accuracy in differentiating cortical from cancellous bone in the metaphyseal region, and thus cannot properly define the intra-medullary region of uncored proximal ulnae. We investigate the geometric dimensions of the proximal ulna intra-medullary cavity using CT studies of cored cadaveric ulnae.


J. Doornberg T. Bosse M. Cohen J. Jupiter D. Ring P. Kloen

Summary

In contrast to the current literature, myofibroblasts are not present in chronic posttraumatic elbow contractures.

However, myofibroblasts are present in the acute phase after an elbow fracture and/or dislocation. This suggests a physiological role in normal capsule healing and a potential role in the early phase of posttraumatic contracture formation.

Introduction

Elbow stiffness is a common complication after elbow trauma. The elbow capsule is often thickened, fibrotic and contracted upon surgical release. The limited studies available suggest that the capsule is contracted because of fibroblast to myofibroblast differentiation. However, the timeline is controversial and data on human capsules are scarce.

We hypothesise that myofibroblasts are absent in normal capsules and early after acute trauma and elevated in patients with posttraumatic elbow contracture.


O. Alizadehkhaiyat G. Kemp S. Frostick

Summary Statement

Applying appropriate upper limb regional-specific and joint-specific tools along with suitable psychologic tools provides an effective assessment of supportive, interventional, and treatment strategies in TE.

Background

Tennis elbow (TE) is a painful pathologic condition with its origin in the common wrist extensor muscles at the lateral epicondyle. As the second most frequently diagnosed musculoskeletal disorder in the neck and upper limb in a primary care setting, with an annual incidence of 4 to 7 cases per 1000 patients in general practice (with a peak at 35 to 54 yrs of age), TE has considerable socioeconomic costs. As pain relief and improvement in functional performance are the 2 common aims of all treatment strategies, the importance of using appropriate tools for the assessment of pain and functional disability in TE is evident. In view of the high prevalence of TE, uncertainties about its treatment, and its substantial socioeconomic consequences, using more specific, patient-centred assessment tools is essential for providing more useful information on the level of pain and functional disability in TE. The Study aimed to: 1) compare pain and functional disability in tennis elbow (TE) patients with healthy controls; and 2) evaluate the relationship between the 2 major psychologic factors (anxiety and depression) and TE.


W. Elliott D. Kaimrajh P. Sawardeker E. Milne A. Ouellette L. Latta

Summary

The significance of matching radius of curvature of the radial head implant and the capitellum in implant selection is evaluated. A mismatch of radius of curvature could lead to point loading, reducing contact area, creating large contact stresses, resulting in arthritis, pain, and other complications.

Introduction

Radial head (RH) implant size is chosen by reconstruction outside of the radiocapitellar joint capsule measuring the RH diameter and length, which is replicated for implant selection. RH radius of curvature (RC) is rarely part of the decision although important in determining contact area.


W. Elliott P. Sawardeker D. Kaimrajh C. Kam E. Milne A. Ouellette L. Latta

Summary

Consistent load distributions with over-sizing of radial head implants show minimal variance in interosseus ligament (IOL) and triangular-fibrocartilage complex (TFCC) tension, both of which are essential in distribution of load at the elbow.

Introduction:Changes in loading distribution at the elbow have not been studied with radial head (RH) arthroplasty. Difficulty arises concerning distribution variability between loading methods and magnitudes, and with implant oversizing.

Method

RC joint capsule were exposed using the Kocher approach in seven fresh-frozen cadaver Humeri. Specimens were loaded axially in an MTS machine with humeri at 90° and wrist neutral. The arms were cycled in load control between 13N–130N until steady-state was reached for each trial. After loading in neutral, the arms were rotated to 60° supination (60S) and 60° pronation (60P), the test repeated. The radial head was excised and Co-Cr implant inserted. Sizings 0mm, +2mm, +4mm were simulated using 2mm plastic spacers on the stem. A Tekscan pressure map transducer at RC recorded loading. The recorded Tekscan loads were organised according to sizing (native, 0mm, +2mm, +4mm) for each specimen. The max/min load values were recorded and the difference, ΔL was calculated. The Max and ΔL values from each sizing were percentage paired with the respective native value. The ΔL values were used to discern load distribution. A linear regression was done using the RC loading plotted against the applied load to visualise the change of load distribution with changing applied loads. Data was analyzed using one-way analysis of variance.


W. Elliott P. Sawardeker C. Kam A. Ouellette L. Latta

Summary

Increased lateral ulnotrochlear joint space due to improper sizing in radial head arthroplasty may result in medial collateral ligament laxity, leading to increased osteophytes and arthritis.

Introduction

Radial head (RH) arthroplasty is a common response to comminuted RH fractures. Typical complications include improper sizing, leading to changes in joint kinematics. Evidence of these changes should be visible through fluoroscopic images of affected joints. The two examined changes in this study are the ulnar deviation from distal radial translation (DRT), and the widening of the lateral ulnotrochlear joint space (LUT).


O. Alizadehkhaiyat K. Vishwanathan S. Frostick

Summary Statement

Discovery system produced effective functional improvement in both primary and revision total elbow replacement. The incidence of major complications was in an acceptable range.

Introduction

The search for the ideal elbow prosthesis continues as instability and loosening remain the prime reasons for total elbow replacement (TER) failure. The Discovery Elbow System (Biomet) is one of the latest generations of linked prosthesis and has been used in UK since 2003. We report outcome of TER using this system.


G. Hendriks R. Senden I.C. Heyligers K. Meijer B. Grimm

Summary

Upper extremity activity was similar in patients and healthy subjects, showing no significant asymmetry between arms within subjects. Further improvements (e.g. thresholds, filters, inclinometer function) are needed to show the clinical value of AM for patients suffering shoulder complaints.

Introduction

Activity monitoring is becoming a popular outcome tool especially in orthopaedics. The suitability of a single 3D acceleration-based activity monitor (AM) for patients with lower-extremity problems has been shown. However less is known about its feasibility to monitor upper-extremity activity. Insight into the amount and intensity of upper-extremity activity of the affected and non-affected arm (asymmetry) may be of added value for diagnostics, therapy choice and evaluating treatment effects. This study investigates the feasibility of a single AM to evaluate (asymmetry in) upper-extremity activity in daily life.


G. Hendriks A. Aquilina R. Senden A. Blom K. Meijer I.C. Heyligers B. Grimm

Summary

A single 3D accelerometer is accurate in measuring upper-extremity activity durations, rest periods and intensities, suggesting its feasibility for daily life measurements with patients. Further enhancements are feasible to reduce residual false classifications of intensity from certain activities.

Introduction

Physical activity is an important outcome measure in orthopaedics as it reflects how surgically restored functional capacity is used in daily life. Accelerometer-based activity monitors (AM) are objective, reliable and valid to determine lower extremity activity in orthopaedic patients. However the suitability of a single AM to monitor upper-extremity activity, in terms of quantity and intensity, has not been investigated. This study investigates the suitability and validity of a single AM to measure quantity and intensity of upper-extremity activity.


L.A. Nasto D. Colangelo C. Sernia E. Di Meco C. Fabbriciani M. Fantoni E. Pola

Summary

Pyogenic spondylodiscitis is an uncommon but severe spinal infection. In majority of cases treatment is based on intravenous antibiotics and rigid brace immobilization. Posterior percutaneous spinal instrumentation is a safe alternative procedure in relieving pain, preventing deformity and neurological compromise.

Introduction

Pyogenic spondylodiscitis (PS) is an uncommon but severe spinal infection. Patients affected by a non-complicated PS and treatment is based on intravenous antibiotics and rigid brace immobilization with a thoracolumbosacral orthosis (TLSO) suffices in most cases in relieving pain, preventing deformity and neurological compromise. Since January 2010 we started offering patients percutaneous posterior screw-rod instrumentation as alternative approach to TLSO immobilization. The aim of this study was to evaluate safety and effectiveness of posterior percutaneous spinal instrumentation for single level lower thoracic (T9-T12) or lumbar pyogenic spondylodiscitis.


P. Bhushan M. Varghese

Summary

There is little consensus regarding the regime for treatment of tuberculosis of spine, although WHO has laid down guidelines couple of years back classifying spinal tuberculosis in Category 1. This study proves the efficacy of WHO regime in spinal tuberculosis by clinico-radiological evaluation.

Introduction

The medical fraternity is divided over the duration of chemotherapy in cases spinal tuberculosis. WHO clearly recommend spinal tuberculosis under Category I, but not accepted by most clinicians.


C. Della Valle G. Candiani D. Pezzoli L. Visai L. Rimondini A. Cochis E. De Giglio S. Cometa F. Bucciotti R. Chiesa

The aim of the work is to develop innovative antibacterial surface modification treatments for titanium capable to limit the bacterial adhesion and proliferation as weel as the biofilm formation while maintaining an high osteointegrative potential. The goal is to contrast the infections which represent a serius complication related to the use of implantable devices.

Introduction

Titanium and titanium alloy are considered the golden standard materials for the applications in contact with bone especially for dental and orthopaedic applications. To extend the implantable component lifetime and increase their clinical performance some surface modifications are required, to promote and speed up the osteointegration process increasing the rate of bone bonding. Unfortunately, among the different complications related to the use of titanium implantable devices the infections represent the most serious, often leading to implant failure and revision. The use of surface modification with specific metal ions represents a promising approach to fight implant-related infections. In particular gallium has recently shown efficacy in the treatment of infections: exploiting the chemical similarity of Ga3+ with Fe3+, it can interfere in the iron metabolism for a wide range of bacteria. The aim of this work is to develop and characterise new biocompatible biomimetic treatments with anodic spark deposition (ASD) technique on titanium characterised by antibacterial properties maintaining high osteointegrative potential.

Experimental Methods

Three surfaces were developed using titanium grade 2 samples (12 mm diam., 0.5 mm thick): i) SiB-Na: ASD treatment performed in an electrolytic solution containing Ca, P, Si and Na1 used as control; ii) GaOss: ASD treatment performed in the SiB-Na solution enriched with gallium nitrate and oxalic acid; iii) GaCis: ASD treatment performed in the SiB-Na solution enriched with with gallium nitrate and L-cysteine. The ASD was carried out in galvano-static condition with a current density of 10 mA/cm2 reaching 295V (for SiB-Na, GaCis) and 310V for GaOss. Untreated Ti was used as control. The surface morphology and chemistry were analysed using SEM, EDS and XPS. Ga release in D-PBS was studied up to 21 days using ICP/OES analysis. The structure of the titanium oxide was investigated using XRD while the surface wettability was studied using OCA measurements. The coating mechanical stability was evaluated using scratch test and three-point bending test. Human osteoblastic cells (Saos2) indirect citotoxicity was asessed using Alamar Blue assay. Saos2 morphology and adhesion to the treated surfaces were evaluated using SEM and actin staining. Saos2 viability was assessed up to 21 of cell cultured in direct contact with antibacterial surfaces while the Saos2 alkaline phosphatase activity (ALP) was evaluated up to 21 day as a marker of new bone formation. The antibacterial properties were assessed with S. mutans, S. epidermidis and E. coli bacterial strains even after 21 days of the antibacterial agents release to test the long lasting antibacterial activity. Also the effectiveness in limiting biofilm formation was evaluated against S. epidermidis and A. baumanni biofilm producers.


H. Aro H. Ahtinen J. Kulkova L. Lindholm E. Eerola A. Hakanen N. Moritz M. Söderström T. Saanijoki A. Roivainen

Summary

Coagulase-negative staphylococci, including S. epidermidis, have emerged as the leading pathogens of hospital-acquired biomaterial-related infections. These infections can be clinically indolent and challenging also for diagnostic imaging. In the current model of catheter-related infections, 68Ga-labeled Siglec-9 PET/CT imaging was able to detect peri-implant S. epidermidis bone infections.

Introduction

Coagulase-negative staphylococci, including S. epidermidis, have emerged as the leading pathogen of nosocomial (hospital-acquired) biomaterial-related infections, including periprosthetic infections and intravascular catheter-related bloodstream infections. Pathogenic S. epidermidis strains exhibit robust attachment to implant surfaces and subsequent biofilm formation. By nature, the clinical picture of periprosthetic S. epidermidis infections can be indolent with vague signs of infection. These infections are also highly challenging for diagnostic imaging and microbiologic studies. Our recent experimental study of 18F-FDG-PET/CT confirmed that subacute peri-implant S. epidermidis infections, reflecting limited inflammatory reaction, are characterised by low 18F-FDG uptake. Vascular adhesion protein-1 (VAP-1) is an inflammation inducible endothelial protein, which controls leukocyte migration to sites of inflammation and infection. Siglec-9 is a leukocyte ligand of VAP-1. We hypothesised that 68Ga-labeled Siglec-9, developed for PET imaging of inflammation and cancer, could be a novel tracer also for early defection of S. epidermidis peri-implant bone infections.


V. Stadelmann I. Potapova K. Camenisch U. Eberli G. Richards F. Moriarty

Summary Statement

In vivo microCT allows monitoring of subtle bone structure changes around infected implants in a rat model.

Introduction

The principal causes of orthopedic implant revisions are periprosthetic bone loss and infections. Immediately after implantation, a dynamic process of bone formation and resorption takes place around an orthopedic implant, influencing its mechanical fixation. Despite its importance, the effect of bacteria on the temporal pattern of periprosthetic remodeling is still unknown. The aim of this study was to evaluate the morphological changes of bone adjacent to an implant in the presence and absence of infection using micro computed tomography (microCT).


I. Potapova E. David M.W. Laschke M. Bischoff R.G. Richards T.F. Moriarty

Summary

The two-step labeling protocol using Lysostaphin and bio-orthogonal click chemistry for staining bacteria is described. The click protocol is efficient in labeling staphylococci and is non-toxic. This protocol promises the efficient of infections that are difficult to assess by conventional imaging.

Introduction

Infection diagnostics in clinics is time consuming, invasive and relays on microbiological cultures. New probes and labeling protocols enabling rapid and specific detection of infection in vivo shall improve the situation. We investigated the potential of a new click labeling protocol to detect staphylococci. Azido (N3) - modified Lysostaphin and DIBO (Di-benzocyclooctyne) - dye were used in the two-step bacteria-labeling protocol. N3 and DIBO were the counterparts of the bioorthogonal “click” reaction. In the first step, Lysostaphin-N3 bound to Staphylococcus aureus. In the second step, N3 clicked to DIBO thus achieving S. aureus selective labeling.


E.T.J. Rochford M. Sabaté Brescó M. Ziegler L. O'Mahoney G. Richards F.T. Moriarty

Summary

An in vivo model of implant infection was developed to assess immune response. Titanium and PEEK implants were tested in the presence of an osteotomy and Staphylococcus aureus contamination. Immune response differed yet the outcome of contamination did not.

Introduction

The presence of an implant increases infection risk by reducing the number of bacteria required to cause an infection. The nature or magnitude of this risk may be influenced by the implant material. A model of implant associated osteomyelitis was developed based upon the MouseFixTM model and the development of infection and immune responses associated with either titanium or PEEK implants was investigated.


V. Post P. Wahl I. Uckay W. Zimmerli S. Corvec C. Loiez P. Ochsner F. Moriarty

Summary

Staphylococcus aureus isolates from Fracture fixation device related infections contained fewer isolates that form a strong biofilm in comparison with isolates from Prosthetic joint infections. Both orthopaedic implant related infection groups possessed fnbB and sdrE more frequently than the non-implant related infection groups.

Introduction

One of the most common pathogen causing musculoskeletal infections is Staphylococcus aureus. The aim was to characterise S. aureus isolated from these infections and to look for differences between the isolates from orthopaedic implant related infections (OIRI) and those in non-implant related infections (NIRI). The OIRI are further differentiated in those associated with fracture fixation (FFI) devices and those found in prosthetic joint infections (PJI).


E. Meani M. Fini G. Giavaresi L. Drago C.L. Romanò

Summary Statement

An Implant Disposable Antibacterial Coating (i-DAC®) is described, consisting of a fully resorbable, biocompatible hydrogel, able to release antibacterial and antibiofilm agents. Direct application of the hydrogel on implants prevented infection occurrence in an in vitro model of peri-prosthetic infection.

Introduction

Biofilm-related infections are among the main reasons for failure of joint prosthesis with high associated social and economical costs. Bacterial adhesion and subsequent biofilm formation have been shown to develop early after biomaterials implant into the human body, when a “race to the surface” takes place between the host's cells and the colonizing bacteria eventually present at the surgical site. Providing an antibacterial/antibiofilm coating of the implant may then play a strategic role in preventing biofilm related infections. Here we report the results of a series of in vitro and in vivo studies, partially performed under the European 7th Framework Programme (Implant Disposable Antibiotic Coating, IDAC, collaborative research project # 277988), concerning a fully resorbable, biocompatible antibacterial hydrogel coating (DAC®, Novagenit, Italy). The patented hydrogel, a co-polimer comprising of hyaluronic acid and a polylactic acid, has been designed to be mixed with various antibacterial agents and applied directly on the implant at the time of surgery, being fully resorbed within few days.


N. Ehrhart R. Rose M. Woodard L. Parkinson L. Chubb

Summary Statement

A single, locally-delivered injection of a human placental product containing multipotent stromal cells reduced severity of infection in an immunosuppressed murine osteomyelitis model and eliminated infection in 25% of animals compared with 0% of controls without the use of antibiotics.

Introduction

Implant–associated osteomyelitis is a serious orthopaedic condition and is particularly difficult to treat in immunosuppressed individuals. Despite great advancement in the field of biomaterials and pharmaceuticals, emerging patterns of antibiotic resistance, complex biofilm production and penetration of therapeutic concentrations of effective antibiotics into bone continue to represent unmet clinical challenges. The promise of adult multipotent stromal cells (MSCs) for tissue regeneration has been of intense interest in recent years. Among their many potential therapeutic uses, MSCs have also been shown to have direct antimicrobial properties. The objective of this study was to evaluate the efficacy of a locally–delivered human placental-based tissue product containing multipotent stromal cells (hAmSC) to reduce the severity of implant-associated Staphylococcus aureus osteomyelitis in an immunosuppressed murine model. We hypothesised that athymic mice with implant-associated osteomyelitis would have diminished infection following treatment with hAmSC as evidenced by decreased bioluminescence intensity and lower histologic scores for infection and bacterial load when compared to saline-treated controls.


J. Lee C. Jeong

Summary Statement

The implantation of scaffold-free CTE from suspension culture into growth-plate defects resulted in a significant reduction in growth arrest of the rabbit tibia

Introduction

In childhood and adolescence, the growth plate injury can cause partial premature arrest of growth plate, which can make problems such as leg length discrepancy and angular deformity. Bone bridge resection and variable implantation materials such as fat, bone wax, silastic and craniopalst has been investigated. However, those procedures may show limitations including the control of bone growth and long term safety of implant materials in vivo. As an alternative, homogeneous or heterogeneous cartilage cells and stem cell transplants have been tried. In this method, scaffold for cell transplantation is needed. But, so far the most suitable scaffold has not been established. Recently, some authors generated a cartilage tissue equivalent (CTE) using a suspension culture with biophysical properties similar to native hyaline cartilage. Therefore we are able to transplant the CTE without scaffold to the physeal defect. The purpose of this study was to investigated the effects of a transplantation of a vitro-generated scaffold-free tissue-engineered cartilage tissue equivalent (CTE) using a suspension chondrocyte culture in a rabbit growth arrest model.


S. Semevolos M. Kinsley K. Duesterdieck-Zellmer T. Riddick

Summary Statement

Differential expression of canonical and noncanonical Wnt signalling along cartilage canals and osteochondral junctions is dependent on age. Increased gene expression of PTHrP along cartilage canals and Ihh along osteochondral junctions suggests paracrine feedback in articular-epiphyseal cartilage.

Introduction

Wnt signaling has been shown to regulate chondrocyte differentiation during pre-/post-natal cartilage development. In addition, parathyroid-related peptide(PTHrP) and Indian hedgehog(Ihh) create a negative feedback loop in growth cartilage, but less is known in articular cartilage. The objective of this study was to elucidate expression of regulatory molecules in chondrocytes surrounding cartilage canals and osteochondral junctions during neonatal and pre-adolescent development. We hypothesised there would be increased expression of canonical Wnt signalling molecules and Ihh in osteochondral junction chondrocytes compared to cartilage canal chondrocytes. In addition, we hypothesised that Wnt signaling and PTHrP expression would be greater in neonates than pre-adolescents.


M. Kogawa K. Khalid A. Wijenayaka R. Ormsby D. Findlay G. Atkins

Introduction

Sclerostin has been implicated in mechanotransduction in bone and recent data show a lack of response to loading in the sclerostin transgenic mouse. Sclerostin, the protein product of the SOST gene, is an attractive therapeutic target for low bone mass conditions, including osteoporosis. It is expressed exclusively by mature osteocytes in bone and we have shown that sclerostin targets pre-osteocytes/osteocytes to regulate bone mineralization and osteoclast activity, as well as inducing catabolic gene expression in osteocytes themselves and promoting osteocyte-mediated bone loss (osteocytic osteolysis). The aim of this study was to examine the direct effects of sclerostin on anabolic responses to loading in bone ex vivo.

Methods

10 × 5mm bovine sternum trabecular bone cores were perfused with osteogenic media at 37°C for up to 3 weeks in individual bone culture chambers. The cores were divided into 3 groups; a) mechanically loaded (300 cycles, 4000 μstrain, 1 Hz/day), b) identical loading regime with continuous perfusion of 50 ng/ml recombinant human sclerostin and c) unloaded controls. Loading was accomplished using a second-generation Zetos™ bone loading system. Daily measurements of bone stiffness (Young's modulus), media pH and ionic calcium concentrations were made. Histomorphometric assessment, including fluorochrome labelling analysis, was made of resin-embedded, non-decalcified samples at the end of the experiment. Gene expression in the bovine bone was examined by real-time RT-PCR.


M. Caron P. Emans D. Surtel A. Cremers L. van Rhijn T. Welting

Summary

Indomethacin has differential effects on chondrogencic outcome depending on differentiation stage

Introduction

Heterotopic ossification (HO) is the abnormal formation of bone in soft tissues and is a frequent complication of hip replacement surgery. The standard treatment to prevent HO is administration of the NSAID indomethacin. HOs are described to develop via endochondral ossification. As it is currently unknown how indomethacin prevents HO, we aimed to define whether indomethacin might influence HO via impairing the chondrogenic phase of endochondral ossification.


A. Calzado-Martín L. Crespo L. Saldaña A. Boré E. Gómez-Barrena N. Vilaboa

Summary

Attachment, proliferation and osteogenic maturation of hMSCs are enhanced on a sub-micron grooved Ti6Al4V alloy, while osteoblasts are less sensitive. These effects are attributed to their different maturation stage and may be mediated through differential activation of the RhoA/ROCK pathway.

Introduction

Ti6Al4V alloy is the most widely used titanium-based biomaterial for manufacturing bone-anchoring devices. We report on the interactions of human bone-forming cells, mesenchymal stem cells from bone marrow (hMSCs) and primary osteoblasts (hOBs), with an anisotropic Ti6Al4V alloy that displays submicron grooves.


Y. Ding J. Huang D. Huang H. Shen

Summary

RNAi targeting p110β reduces TNF-alpha production and osteolysis in response to wear particles.

Introduction

Aseptic joint loosening is a key factor that reduces the life span of joint prosthesis. Prosthetic wear particles are thought to play a central role in the initiation and development of periprosthetic osteolysis, leading to aseptic loosening of prostheses. This study aims to explore the effect of p110β-targeted small interfering RNA (siRNA) and lentivirus on particle-induced inflammatory cytokine expression in murine macrophage.


H. Lawrence D. Deehan J. Holland J. Kirby A. Tyson-Capper

Summary

Metal-on-metal hip replacements have been associated with adverse reactions including inflammatory pseudotumours and soft tissue necrosis. We have shown that cobalt can directly activate toll-like receptor 4, an immune receptor causing pro-inflammatory interleukin-8 secretion. This may contribute to adverse reaction development.

Introduction

Metal-on-metal hips have the highest failure rate of any joint arthroplasty material. Reasons for failure include the development of pseudotumours, soft tissue necrosis and pain around the affected joint. The adverse reactions appear to be inflammatory as failing joints are often infiltrated by immune cells such as lymphocytes. However the exact cellular and biological mechanisms underlying this inflammation are unknown. Toll-like receptor 4 (TLR4) is found on the surface of immune cells including macrophages and dendritic cells. It is activated by lipopolysaccharide (LPS) from Gram negative bacteria, inducing an immune response against the pathogen through increased secretion of pro-inflammatory cytokines. It has recently been shown that nickel can activate TLR4, causing inflammation. Cobalt, a component of many metal-on-metal joints, is adjacent to nickel in the periodic table and shares a number of nickel's properties. Consequently we hypothesised that cobalt ions from metal-on-metal joints can activate TLR4.


T. Yasuda

Summary

Hyaluronan suppressed lipopolysaccharide-stimulated prostaglandin E2 production via intercellular adhesion molecule-1 through down-regulation of nuclear factor-κB. Administration of hyaluronan into rheumatoid joints may decrease prostaglandin E2 production by activated macrophages, which could result in improvement of arthritic pain.

Introduction

Prostaglandin E2 (PGE2) is one of the key mediators of inflammation in rheumatoid arthritis (RA) joints. Intra-articular injection of high molecular weight hyaluronan (HA) into RA knee joints relieves arthritic pain. Although HA has been shown to inhibit PGE2 production in cytokine-stimulated synovial fibroblasts, it remains unclear how HA suppresses PGE2 production in catabolically activated cells. Furthermore, HA effect on macrophages has rarely been investigated in spite of their contribution to RA joint pathology.


R.L. Williams N.M. Salimi G.A. Leeke R.H. Bridson L.M. Grover

Summary Statement

Calcium phosphate (CaP) particles have attracted great interest as transfection reagents, yet little is known about their mechanism of internalisation. We report live cell time-course tracking of CaP particles during internalisation and the influence of Ca:P ratio on transfection efficiency.

Introduction

Relatively recent work has seen calcium phosphate (CaP) salts used for the delivery of biological materials into cells in the form of peptides, polymers and DNA sequences. Calcium phosphate salts have a critical safety advantage over other vectors such as viruses in that they pose no risk of pathogenicity due to mutation and show no apparent cytotoxicity. Previous work within the group showed that Ca:P ratio influenced the transfection efficiency, but the fate of the particles on internalisation is yet unknown. The difficulty in tracking the particles can be related to the visual similarity to granulation within the cells. Using a surface modification method that enables the fluorescent labeling of silicon-substituted hydroxyapatite (SiHA) particles, we have tracked the internalisation of the particles to understand their mechanism of entry and how particle composition may influence transfection efficiency.


P. Walsh K. Mulhall

Summary Statement

Ischaemic preconditioning protected skeletal myotubes against the effects of ischaemia-reperfusion in vitro. This protection was associated with increased Nrf2 signalling.

Introduction

Ischaemic preconditioning (IPC) is a well recognised and powerful phenomenon where a tissue becomes more tolerant to a period of prolonged ischaemia when it is first subjected to short bursts of ischaemia/reperfusion. While much is known about the ability of ischaemic preconditioning to protect myocardial tissue against ischaemia-reperfusion injury, its potential to confer benefit in an orthopaedic setting by protecting skeletal muscle remains relatively unexplored to date.

One mechanism by which ischaemic preconditioning may induce protection is through a reduction in oxidative stress. Reactive oxygen species (ROS) are generated both during prolonged ischaemia and also upon reperfusion by infiltrating neutrophils, thereby leading to an increase in oxidative stress. The transcription factor, NF-E2-related factor 2 (Nrf2), is a key regulator of the cells response to oxidative stress as it regulates the expression of a network of anti-oxidant/detoxifying enzymes. Nrf2 signalling has recently been shown to protect against ischaemia-reperfusion injury in both a kidney cell line and in liver biopsies, indicating that this transcription factor may play a key role in the protection provided by ischaemic preconditioning. To date, the involvement of Nrf2 in the response of skeletal muscle to ischaemia-reperfusion has not been investigated. Thus, the aims of this study were to investigate the ability of ischaemic preconditioning to protect skeletal myotubes against ischaemia-reperfusion and to determine the role of Nrf2 signalling in this protection.


G. Liu B. Tan D. Riew H.K. Wong

Summary Statement

Tandem stenosis is a prevalent condition in an Asian population with the narrowest cervical canal diameters and risk factors include advanced age and increased levels of lumbar canal stenosis.

Introduction

Tandem spinal stenosis (TSS) is defined as patient with concomitant spinal canal stenosis found in both cervical (C) and lumbar (L) spinal region. Few studies have reported the incidence of TSS is ranged from 5–25%, but these are all noncomparative, small cohort studies. To the best of author knowledge this is the 1st study aims to compare the prevalence of TSS and its risk factors of development in a large multiracial Asian population.


C. Barrios E. Montes J. Burgos G. de Blas M. Antón-Rodrigálvarez E. Hevia C. Correa

Summary Statement

The spinal cord showed marked sensibility to acute compression causing complete and irreversible injury. On the contrary, the spinal cord has more ability for adaptation to slow progressive compression mechanisms having the possibility of neural recovery after compression release.

Introduction

The aim of this experimental study was to establish, by means of neurophysiologic monitoring, the degree of compression needed to cause neurologic injury to the spinal cord, and analyze whether these limits are different making fast or slow compression.


R. Llombart-Blanco R. Llombart-Ais C. Barrios J.L. Beguiristain

Summary Statement

Bilaretal epiphysiodesis of he neurocentral cartilages causes shortening of the sagittal length of the pedicles and a subsequent spinal stenosis at the operated segments, resembling that found in patients with achrondroplasia.

Introduction

The introduction of pedicle screws in the immature spine may have implications for the growth of the vertebra. The effect of blocking the growth of neurocentral cartilage (NC) is not yet fully defined. Block hypothetically leads to a bilateral symmetrical alteration of the vertebral growth. Using an experimental animal model, our goal is to analyze if a bilateral epiphysiodesis of the NC using pedicle screws is able to induce narrowing of the spinal canal in the thoracolumbar spine.


J. Daniels K.L.E. Phillips A.L.A. Binch N. Chiverton L. Breakwell A.R. Micheal A. Cole S.L. Dunn C.L. Le Maitre

Summary

Anabolic and catabolic signalling processes within IVDs display overlapping pathways, however some pathways were identified as selective to catabolic signalling and inhibition of one of these pathways inhibited some of the catabolic factors induced by IL-1 although NFkB inhibition also affected anabolic expression.

Degeneration of intervertebral discs (IVDs) is implicated in 40% of low back pain cases. In the normal disc the balance between anabolic and catabolic processes are carefully balanced. During degeneration this balance is lost in favour of catabolic processes which lead to degradation of the IVD, infiltration of blood vessels and nerves and release of cytokines which sensitise nerves to pain. Interleukin 1 (IL-1) is known to be important in the pathogenesis of IVD degeneration, here we investigated the intracellular signalling pathways activated by IL-1 and those activated by an anabolic factor (CDMP-1) to investigate differential pathways.

Human nucleus pulposus cells (NP) removed during discetomy for nerve root pain were stimulated with IL-1 or CDMP-1 for 30 minutes. Site-specific phosphorylation of 46 signalling molecules were identified using R&D proteome array. The activation of ERK1/2, p38, c-jun, and IkB were confirmed using cell based ELISAs, in addition pNFκB localisation in stimulated cells was determined using immunohistochemisty. Pre-treatment with inhibitors to p38, and NFkB for 30 minutes, followed by stimulation with IL-1 (10ng/mL) or CDMP-1 (10ng/mL) for 24 hours was investigated to determine effects on anabolic and catabolic factors. In addition localisation of phosphorylated c-jun, p38 and NFkB were investigated within paraffin embedded sections of human IVD to investigate the presence of active pathways in vivo.

Twenty intracellular signalling pathways were activated following CDMP-1 treatment and 8 signalling pathways activated by IL-1. Of note key classical IL-1 signalling pathways p38 MAPK, ERK 1/2 and JNK were activated by IL-1, however of these ERK 1/2 particularly was also activated by CDMP-1, whilst p38 and c-jun were only activated by IL-1. IL-1 induced activation of NFkB signalling to a greater extent than CDMP-1, these results were confirmed by the ‘in cell ELISAs’. IVD tissue samples displayed immunopositive staining for phosphorylated c-jun, NFkB and p38. Inhibition of p38 signalling inhibited IL-1 induced MMP 13 expression, but had little effect on the induction of IL-8. However inhibitors of NFkB signalling pathway failed to inhibit the induction of MMP 13 but abrogated the induced IL-6 and IL-8 expression. IL-1 induced a complete aberration of aggrecan expression by NP cells in alginate culture, this effect was partly inhibited by p38 MAPK inhibitor but was completely restored by inhibiting NFkB signalling. However the aggrecan expressed in CDMP-1 treated cells was decreased by inhibiting NFkB but not p38.

Here, we have shown that anabolic and catabolic signalling processes within IVDs show a number of overlapping pathways, however a number of differential pathways were identified and inhibition of p38 MAPK and NFkB pathways inhibited a number of catabolic processes investigated which were induced by IL-1. Thus inhibition of signalling pathways could be a novel mechanism of inhibiting catabolic processes which could hold promise to inhibit degeneration at early stages of disease but also create the correct tissue niche to promote regeneration of the disc.


T. Miyakawa T. Takebayashi Y. Terasima I. Ohgon T. Yamashita

Summary Statement

TRPA1 antagonist reduced spontaneous excitatory postsynaptic currents of substantia gelatinosa neuron in spinal cord dorsal horn by in vivo patch-clamp analysis. TRPA1 may act as a mediator of excitatory synaptic transmission.

Introduction

Little is known about the pathophysiological mechanisms of radicular pain. The substantia gelatinosa (SG) in the spinal cord dorsal horn receives primary afferent inputs, which predominantly convey nociceptive sensations. Nociceptive information is modified and integrated in the SG, suggesting that the SG may be a therapeutic target for treating radicular pain. Electrophysiological study using in vivo patch-clamp recording from SG neurons is a useful method to analyze functional properties in synaptic transmission. Transient receptor potential ankyrin 1 (TRPA1) has been widely identified in the central and peripheral nervous system such as peripheral nociceptor, dorsal root ganglion (DRG), and spinal cord dorsal horn, and is considered that they are involved in synaptic transmission of pain. However, it is still unknown about its functional role and mechanism of pain transmission in spinal cord dorsal horn. The purpose of this study is to investigate changes in excitatory synaptic transmission of SG neurons with TRPA1 antagonist and to clarify the potential role of TRPA1 in the rat spinal cord dorsal horn using in vivo patch-clamp analysis.


N. Schizas B. Andersson N. Hailer

Summary Statement

Spinal cord injury is characterised by an inflammatory cascade that leads to neuronal death by neurotoxicity. In a model of spinal cord damage we successfully preserved the number of ventral horn neurons by treatment with interleukin-1 receptor antagonist (IL1RA) and neurotrophin (NT)-3.

Introduction

Secondary damage after spinal cord injury (SCI) is characterised by activation of microglial cells that release neurotoxic agents. This results in apoptotic death of neurons that survived the initial trauma. Interleukin (IL)-1 is one of the most prominent mediators of neurotoxicity. Organotypic spinal cord slice cultures (OSCSC) are a useful in vitro model of spinal cord injury. We have previously shown that OSCSC degenerate substantially during in vitro incubation under standard conditions. Our aim was to treat OSCSC with the putatively neuroprotective agents IL-1 receptor antagonist (IL1RA) and neurotrophin (NT)-3 and to evaluate neuronal and microglial populations as well as axonal preservation. We hypothesised that treatment with the above substances would enhance neuronal survival and suppress microglial activation.


C. Lam P. Assinck J. Liu W. Tetzlaff T. Oxland

Summary Statement

The mechanism of spinal cord injury varies across the human population and this may be important for the development of effective therapies. Therefore, detailed understanding of how variables such as impact velocity and depth affect cord tissue damage is important.

Introduction

Studies have shown an independent effect of impact velocity and depth on injury severity, thereby suggesting importance of the interaction between the two for spinal cord injury. This work examines both the individual and interactive effects of impact velocity and impact depth on demyelination, tissue sparing, and behavioural outcomes in the rat cervical spinal cord. It also aims to understand the contribution of the energy applied during impact, not only the impact factors. Decoupling the effects of these two impact parameters will help to describe the injury mechanism. Maximum principal strain has also been shown to be useful as a predictor for neural tissue damage in vivo and in finite element (FE) models. A better understanding of this relationship with experimental results may help to elucidate the mechanics of spinal cord injury.


M. Peroglio D. Eglin L. Benneker M. Alini S. Grad

Summary

Carriers for local delivery of stem cells into degenerative intervertebral discs need to be tested under physiological loading since stem cell viability, density and differentiation, as well as carrier stability are strongly affected by loading.

Introduction

The success of the local delivery of mesenchymal stem cells (MSCs) to degenerative discs relies on three main factors: (i) an appropriate delivery method, (ii) a suitable carrier, (iii) resistance to loading forces. Bioreactors allow the application of loading to whole intervertebral discs and represent a useful tool to screen the potential of new regenerative therapies. We have previously shown that hydrogel delivery through the endplate (EP) leaves the annulus fibrosus (AF) intact (as opposed to an approach through the AF). Furthermore, we have found that the physiological loading needs to be adapted for nucleotomised discs. In this study we compare the behaviour of two MSCs carriers under loading in a whole IVD bioreactor.


J. Roh C. Yeung J. Field

Summary

In this study, OsteoAMP® bone graft showed superior fusion rates as compared to rhBMP-2 at all timepoints (p<0.004). Additionally, OsteoAMP® bone graft had >80% few adverse events as compared to rhBMP-2.

Introduction

Adverse events and complications related to use of rhBMP-2 have raised many ethical, legal, and reimbursement concerns for surgeons. OsteoAMP® bone graft is an allograft derived growth factor, rich in osteoinductive, angiogenic, and mitogenic proteins. The following data displays a blinded, multi -center study evaluating and comparing fusion outcomes between rhBMP-2 and OsteoAMP® bone graft.


A. Roth R. Bogie P. Willems T. Welting C. Arts L. van Rhijn

Summary Statement

Novel radiopaque UHMWPE sublaminar cables may be a promising alternative to gliding pedicle screws or titanium sublaminar cables within a growth-guidance system for the surgical treatment of early onset scoliosis.

Introduction

Growth-guidance or self-lengthening rod systems are an alternative to subcutaneous growing rods and the vertical expandable prosthetic titanium rib for the treatment of early onset scoliosis. Their main perceived advantage over growing rods is the marked decrease in subsequent operative procedures. The Shilla growth-guidance system and a modern Luque trolley are examples of such systems; both depend on gliding pedicle screws and/or sliding titanium sublaminar wires. However, the unknown consequences of metal-on-metal wear debris are reason for concern especially in young patients. In this study, instrumentation stability, residual growth in the operated segment after surgery and biocompatibility of the novel radiopaque UHMWPE cables as an alternative to gliding pedicles screws or titanium sublaminar wires were assessed in an immature sheep model.


G. Vadalà F. Russo G. Pattappa M. Peroglio S. Grad V. Stadelmann M. Alini V. Denaro

Summary Statement

To test regenerative therapies for the intervertebral disc it is necessary to create a cavity in the nucleus polposus mantaining the annulus fibrosus intact. The transpedicular mechanical nucleotomy represents the best method for this purpose.

Introduction

New cells/hydrogel based treatments for intervertebral disc (IVD) regeneration need to be tested on animal models before clinical translation. Ovine IVD represents a good model but doesn't allow the injection of a significant volume into intact IVD.

The objective of the study was to compare different methods to create a cavity into ovine nucleus pulposus (NP) by enzymatic digestion (E), mechanical discectomy (M) and a combination of both (E+M), as a model to study IVD regeneration strategies with intact anulus fibrosus (AF).


Full Access
D.M. Chetan

Introduction

Hand tumors are usually rare and there is not much literature about series of cases. We have studied a series of 110 cases. Hand tumors do consists of both benign and malignant cases.

Methods

We studied series of 110 cases at Karnataka Institute of Medical Sciences, Hubli and Mysore Medical College & Research Institute, Mysore. We retrospectively reviewed the records of 110 patients who underwent double ray amputations at our center over few years: few had amputations of the fourth and fifth rays and others amputation of the second and third rays. Mean age at surgery was 34 years (range, 10–45 years), and minimum follow up was 64 months (mean, 98 months; range, 64–136 months). Some patients had high-grade soft tissue sarcomas of the hand, synovial sarcomas, malignant peripheral nerve sheath tumors, and undifferentiated sarcoma. No patients had detectable metastases at surgery.


P. Pezeshki M. Akens J. Woo C. Whyne A. Yee

Summary

A novel bipolar cooled radiofrequency ablation probe, optimised for bone metastases applications, is shown in two preclinical models to offer a safe and minimally invasive treatment option that can ablate large tissue volumes and preserve the regenerative ability of bone.

Introduction

Use of radiofrequency ablation (RFA) in treating of skeletal metastases has been rising, yet its impact on bone tissue is poorly understood. 2–11 RF treatment induces frictional heating and effectively necrotises tissue in a local and minimally invasive manner.1 Bipolar cooled RF (BCRF) is a significant improvement to conventional RF whereby larger regions can be safely treated, protecting sensitive neighbouring tissues from thermal effects. This study aimed to evaluate the safety and feasibility of a novel bipolar RFA probe to create large contained lesions within healthy pig vertebrae and its determine its effects on bone and tumour cells in a rabbit long bone tumour model.


Y. Chen B.C. Tai D. Nayak N. Kumar R. Goy H.K. Wong

Summary

Our meta-analysis showed that pooled mean blood loss during spinal tumour surgeries was 2180 ml. Standardised methods of calculating and reporting intra-operative blood loss are needed as it would be beneficial in the pre-operative planning of blood replenishment during surgery.

Introduction

The vertebral column is the commonest site of bony metastasis, accounting for 18,000 new cases in North America yearly. Patients with spinal metastasis are often elderly, have compromised cardiovascular status, poor physiological reserve and altered immune status, all of which render them more susceptible to the complications of intra-operative blood loss and associated transfusion. Currently no consensus exists regarding the expected volume of blood lost during metastatic spine tumour surgery with various papers quoting anywhere between 1L to 6L. Knowledge of the expected blood loss prior to surgery however is important as it facilitates pre-operative planning, intra- and post-operative management of fluid balance and blood transfusion. We conducted a meta-analysis of published literature on spine tumour surgery to answer the question: “What is the expected blood loss in major spinal tumour surgery for metastatic spinal disease?”


N. Kumar Y. Chen Q. Ahmed V. Lee H.K. Wong

Summary

This is the first ever study to report the successful elimination of malignant cells from salvaged blood obtained during metastatic spine tumour surgery using a leucocyte depletion filter.

Introduction

Catastrophic bleeding is a significant problem in metastatic spine tumour surgery (MSTS). However, intaoperative cell salvage (IOCS) has traditionally been contraindicated in tumour surgery because of the theoretical concern of promoting tumour dissemination by re-infusing tumour cells into the circulation. Although IOCS has been extensively investigated in patients undergoing surgery for gynaecological, lung, urological, gastrointestinal, and hepatobiliary cancers, to date, there is no prior report of the use of IOCS in MSTS. We conducted a prospective observational study to evaluate whether LDF can eliminate tumour cells from blood salvaged during MSTS.


N. Kumar Y. Chen A.S. Zaw Q. Ahmed R. Soong D. Nayak H.K. Wong

Summary

There is emerging evidence of successful application of IOCS and leucocyte depletion filter in removing tumour cells from blood salvaged during various oncological surgeries. Research on the use of IOCS-LDF in MSTS is urgently needed.

Introduction

Intra-operative cell salvage (IOCS) can reduce allogeneic blood transfusion requirements in non-tumour related spinal surgery. However, IOCS is deemed contraindicated in metastatic spine tumor surgery (MSTS) due to risk of tumour dissemination. Evidence is emerging from different surgical specialties describing the use of IOCS in cancer surgery. We wanted to investigate if IOCS is really contraindicated in MSTS. We hereby present a systematic literature review to answer the following questions: 1. Has IOCS ever been used in MSTS? 2. Is there any evidence to support the use of IOCS in other oncologic surgeries?


R. Malhotra N. Kumar P.H. Wu A.S. Zaw G. Liu J. Thambiah H.K. Wong

Summary

Metastatic spinal disease is a common entity of much debate in terms of ideal surgical treatment. The introduction of MIS can be a game-changer in the treatment of MSD due to less peri-operative morbidity and allowing earlier radiotherapy and/or chemotherapy.

Introduction

Less invasive techniques have always been welcome for management of patients with ‘Metastatic Spinal Disorders’. This is because these patients can be poor candidates for extensive / major invasive surgery even though radiologically, there may be an indication for one. The aim of the treatment with Minimal Invasive Fixation (MIS) systems is mainly for ‘pain relief’ than to radically decrease tumour burden or to achieve near total spinal cord decompression, which could be major presentations in these patients. These procedures address the ‘spinal instability’ very well and they can address pain associated with compression fractures resulting from metastatic disease from a solid organ as well as multiple myeloma with minimal complications. These procedures can be combined with radiology and chemotherapy without much concern for wound problems in the way of infection or dehiscence. They also have a great advantage of timing of adjunct therapy closer to the index procedure. The disadvantage, however, are they do not allow thorough decompression of the spinal cord. There could also be problem in addressing patients who have severe vertebral height loss or loss of integrity of the anterior column where anterior column reconstruction may be required. There is a risk of inadequate fixation or implant loosening or failure. We aim to examine the results of MIS surgery in our department and support the rationale for its use.


J. Tan J. Lim Y. Chen N. Kumar

Summary

Neurological deficits resulting from spinal cord compression occur infrequently. When presented with neurological compromise, the most common management was radiotherapy, with surgery only being offered to patients who developed neurological deficit or pathological fracture resulting in unresolved severe pain post radiotherapy.

Introduction

Nasopharyngeal carcinoma has been reported to have a higher incidence of distant metastases to the spine. This study was conducted to evaluate the incidence, presentation and management of neurological involvement related to spinal metastasis from nasopharyngeal carcinoma.


R.R. Nadhanan C.-M. Fan Y.-W. Su P. Howe C. Xian

Summary

Methotrexate chemotherapy (commonly used in treating cancers and rheumatoid arthritis) creates an inflammatory condition in bone, decreasing osteogenesis, enhancing adipogenesis, increasing osteoclastogenesis, leading to bone loss and marrow adiposity; treatment with fish oil or folinic acid counteracts these negative effects and prevents bone loss.

Introduction

Chemotherapy with anti-metabolite methotrexate (MTX) is commonly used in treating cancers and rheumatoid arthritis; however it is known to cause bone loss for which currently there are no adjunct preventative treatments.


Y. Dhooge N. Wentink L. Theelen W. van Hemert R. Senden

Summary

The ankle X-ray has moderate diagnostic power to identify syndesmotic instability, showing large sensitivity ranges between observers. Classification systems and radiographic measurements showed moderate to high interobserver agreement, with extended classifications performing worse.

Introduction

There is no consensus regarding the diagnosis and treatment of ankle fractures with respect to syndesmotic injury. The diagnosis of syndesmotic injury is currently based on intraoperative findings. Surgical indication is mainly made by ankle X-ray assessment, by several classification systems and radiographic measurements. Misdiagnosis of the injury results in suboptimal treatment, which may lead to chronic complaints, like instability and osteoarthritis. This study investigates the diagnostic power and interobserver agreement of three classification methods and radiographic measures, currently used to assess X-ankles and to identify syndesmotic injury.


S. Hasegawa J. Mizutani S. Otsuka N. Suzuki M. Fukuoka T. Otsuka S. Banks

Summary

Bi-plane Image matching method is very useful technique to evaluate the loaded 3D motion of each cervical level.

Introduction

Cervical orthoses are commonly used to regulate the motion of cervical spines for conservative treatment of injuries and for post-operative immobilization. Previous studies have reported the efficacy of orthoses for 2D flex-extension or 3D motions of the entire cervical spine. However, the ability of cervical orthoses to reduce motion might be different at each intervertebral level and for different types of motion (flexion-extension, rotation, lateral bending). The effectiveness of immobilizing orthoses at each cervical intervertebral level for 3D motions has not been reported. The purpose of this study is to evaluate the effectiveness of the Philadelphia collar to each level of cervical spines with 3D motion analysis under loading condition.


L. Mangnus D. Meijer J. Mellema W. Veltman E. Steller S. Stufkens J. Doornberg

Summary

Quantification of Three-Dimensional Computed Tomography (Q3DCT) is a reliable and reproducible technique to quantify and characterise ankle fractures with a posterior malleolar fragment (www.traumaplatform.org). This technique could be useful to characterise posterior malleolar fragments associated with specific ankle fracture patterns.

Introduction

Fixation of posterior malleolar fractures of the ankle is subject of ongoing debate1. Fracture fixation is recommended for fragments involving 25–30% of articular surface1. However, these measurements -and this recommendation- are based on plain lateral radiographs only. A reliable and reproducible method for measurements of fragment size and articular involvement of posterior malleolar fractures has not been described. The aim of this study is to assess the inter-observer reliability of Quantification using Three-Dimensional Computed Tomography (Q3DCT) –modelling2,3,4,5 for fragment size and articular involvement of posterior malleolar fractures. We hypothesize that Q3DCT-modelling for posterior malleolar fractures has good to excellent reliability.


V. Povoroznyuk D. Hans N. Dzerovych

Introduction

Trabecular bone score (TBS) is a parameter of bone microarchitecture that is determined by the level analysis of DXA images. TBS is associated with fractures in the preliminary case-control and prospective studies.

The aim of this study was to assess the TBS role in the traumatology and orthopedics.

Materials and methods

We've examined 176 healthy women aged 40–79 years (mean age – 53.4±0.6 yrs) and 117 men aged 40–79 years (mean age – 59.8±0.9 yrs). Bone mineral density (BMD) of whole body, PA lumbar spine and proximal femur were measured by DXA method (Prodigy, GEHC Lunar, Madison, WI, USA) and PA spine TBS were assessed by TBS iNsight® software package installed on the available DXA machine (Med-Imaps, Pessac, France).


A. Parish K. Hing G. Davis

Summary Statement

The structure of bone inside a porous bone graft substitute can be quantified and compared by using a combination of novel measurements of surface area and connectivity. This allows for a numerical representation of the bone structure to be calculated.

Introduction

Variation in absolute bone volume as a function of bone graft porosity has been well documented. However quantification of the 3D shape of bone and it's connectivity has always been difficult to assess let alone quantify. By use of novel computational methods the shape and connectivity of the bone can be characterised giving more insight to the relative quality of the bone ingrowth within the different porous grafts.


A. Aframian O. Jindasa K.S. Khor P. Vinayakam S. Spencer P.J.S. Jeer

Summary

Nearly one-third of patients in this series with an ACL rupture requiring reconstruction had evidence of MPFL injury. This should be considered when patients are seen, and when MRI scans are reviewed/reported.

Introduction

The Medial Patello-Femoral Ligament (MPFL) is the largest component of the medial parapatellar ligamentous complex. The senior surgeon felt that there was an anecdotally high rate of MPFL injury amongst his patients undergoing Anterior Cruciate Ligament (ACL) repair, but no discussion of this in the present literature.


X. Kang D. Wilson A. Hodgson

Summary

We found good to excellent reproducibility of in vivo hip joint angle measurements during repeated sitting when derived from registering low-resolution Open MRI imagesets with a reference high-resolution conventional MRI scan, despite only moderate similarity of the segmented volumes.

Keywords: hip, kinematics, MRI, femoroacetabular impingement, repeatability

Introduction

Femoroacetabular impingement (FAI) is a mechanical hip disorder caused by an abnormal bony contact between the femur and acetabulum. Open MRIs can enable studies of FAI under weightbearing, but the resolution of such scans is comparatively low, so it is useful to obtain high resolution (HR) reference scans from a conventional MRI and register lower resolution (LR) open MRI images to the HR images. The purpose of this study was to establish the degree of correspondence between the segmented volumes from the two types of scanner and to estimate the repeatability of joint angle measurements.


M. Frame

Summary Statement

We are taking very expensive cutting edge technology, usually reserved for industry, and using it with the help of open source free software and a cloud 3D printing services to produce custom and anatomically unique patient individual implants for only £32. This is approx. 1/100th of the traditional cost of implant production.

Introduction

3D printing and rapid prototyping in surgery is an expanding technology. It is often used for preoperative planning, procedure rehearsal and patient education. There have been recent advances in orthopaedic surgery for the development of patient specific guides and jigs. The logical next step as the technology advances is the production of custom orthopaedic implants. Our aim was to use freely available open source software, a personal computer and consumer access online cloud 3D printing services to produce an accurate patient specific orthopaedic implant without utilising specialist expertise, capital expenditure on specialist equipment or the involvement of traditional implant manufacturing companies. This was all to be done quickly, cost effectively and in department.


T. Felka S. Zouhair S. Bast K. Struck L. Handl M. Votteler U. Stoeckle V. Schmidt K. Schenke-Layland A. Grodzinsky B. Rolauffs

Summary

In adult articular cartilage, the pericellular matrix (PCM) mediates chondrocyte-matrix-interactions and is associated with the spatial cellular organization. Immunofluorescence microscopy, multiphoton-induced autofluorescence and second harmonic generation (SHG) imaging, as well as point pattern analyses revealed that both PCM and spatial organization were absent in fetal chondrocytes.

Introduction

In adult articular cartilage, the pericellular matrix mediates the biomechanical, biophysical and biomechanical interactions between the chondrocyte and the extracellular matrix. The PCM is also associated with the spatial organization of human superficial chondrocytes, which are situated in four distinct patterns of strings, clusters, pairs or single cells. However, little is known about the PCM and the spatial organization during fetal development. In this study, we asked the question whether fetal chondrocytes display a spatial organization comparable to that of adult chondrocytes, and whether a PCM is present or absent in the early stages of fetal cartilage development.


A. Marmotti S. Mattia D. E. Bonasia M. Bruzzone S. Terrando C. Tarella E. Ponzo D. Blonna F. Castoldi G. M. Peretti R. Rossi

Summary Statement

Hypoxia enhances chondrocyte phenotype of cells migrating from cartilage fragments, thus supporting the use of chondral fragment as a potential cell source for one-stage cartilage repair

Introduction

Minced cartilage fragments are a viable cell source for one stage cartilage repair, as shown in both in preclinical and clinical studies. However, the joint microenvironment, in which the repair process takes place, is hypoxic and no evidences are present in literature regarding the behaviour of cartilage fragments in a hypoxic environment. Aim of the study is to verify if hypoxia could influence chondrocyte outgrowth from cartilage fragments into a Hyaluronic-Acid/fibrin scaffold and evaluate its effects on migrating chondrocyte behaviour, compared to normoxic condition. This could be significant in the perspective of a wide clinical application of human chondral fragments for single stage repair.


S. Dunn A. Crawford M. Wilkinson R.A.D. Bunning C.L. Le Maitre

Summary Statement

IL-1β stimulation of human OA chondrocytes induces NFκB, ERK1/2, c-JUN, IκB and P38 signalling pathways. Pre-treatment with cannabinoid WIN-55 for 48 hours inhibits certain pathways, providing mechanisms for cannabinoids inhibitory actions on IL-1β induced cartilage degradation.

Matrix metalloproteinases (MMPs) are involved in extracellular matrix (ECM) breakdown in osteoarthritis (OA) and their expression is regulated by nuclear factor kappa B (NFκB). In addition signalling pathways ERK1/2, c-JUN, IκB and P38 are activated in OA and are induced by inflammatory cytokine interleukin 1 (IL-1). Cannabinoids have been shown to reduce joint damage in animal models of arthritis. Synthetic cannabinoid WIN-55, 212-2 mesylate (WIN-55) significantly reduces IL-1β induced expression of MMP-3 and -13 in human OA chondrocytes, indicating a possible mechanism via which cannabinoids may act to prevent ECM breakdown. Here the effects of WIN-55 on IL-1β induced NFκB, ERK1/2, c-JUN, IκB and P38 phosphorylation in human OA chondrocytes has been investigated.

Primary human chondrocytes were obtained from articular cartilage removed from patients with symptomatic OA during total knee replacement (Ethic approval:SMB002). Cartilage tissue was graded macroscopically 0–4 using the Outerbridge Classification method. Chondrocytes isolated from grade 2 cartilage and cultured in monolayer were pre-treated with 10 μM WIN-55 for 1 hour prior to stimulation with 10 ng/ml IL-1β for 30 minutes for investigation of NFκB, c-JUN, IκB and P38 phosphorylation. In addition chondrocytes were pre-treated with 10 μM WIN-55 for 30 minutes, 1, 3, 6, 24 and 48 hours prior to 10 ng/ml IL-1β stimulation for 30 minutes to investigate ERK1/2 phosphorylation.

Dimethyl sulfoxide (DMSO) was used as a vehicle control at 0.1%. Immunocytochemistry was used to investigate the phosphorylation and translocation of NFκB. ERK1/2, c-JUN, IκB, and P38 activation was investigated using cell based ELISA. Immunocytochemical analysis showed chondrocytes stimulated with IL-1β induced NFκB phosphorylation and translocation to the nucleus.

Chondrocytes treated with IL-1β with WIN-55 for 1 hour pre-treatment showed no inhibition of the IL-1β induced NFκB phosphorylation and translocation to the nucleus. WIN-55 treatment alone for 1 hour stimulated NFκB phosphorylation in the cytoplasm but not the nucleus. ELISA showed that phosphorylation of ERK1/2, c-JUN, IκB, and P38 was significantly induced by IL-1β following 30 minutes stimulation (p<0.05). Pre-treatment with WIN-55 for 1 hour had no significant effect on this IL-1β induced phosphorylation. However WIN-55 pre-treatment for 48 hours prior to IL-1β stimulation for 30 minutes, resulted in a significant decrease in ERK1/2 phosphorylation compared to IL-1β stimulation alone (p<0.05).

WIN-55 treatment alone for 1 hour significantly induced c-JUN phosphorylation (p<0.05), but had no effect on IκB and P38 phosphorylation compared to DMSO control. IL-1β stimulation of ERK1/2 phosphorylation was not significantly affected by WIN-55 pre-treatment of 30 minutes, 1, 3, 6 and 24 hours. WIN-55 treatment alone for 48 hours significantly reduced ERK1/2 phosphorylation compared to DMSO control (p<0.05). WIN-55 treatment alone for 30 min, 1, 3, 6 and 24 hours had no significant effect on ERK1/2 phosphorylation compared to DMSO control. The results show that following 48 hours pre-treatment WIN-55 inhibits IL-1β induced ERK1/2 phosphorylation in human OA chondrocytes. Thus inhibitory effects of cannabinoids on IL-1β induced cartilage degradation may be mediated via modulation of ERK1/2 signalling.


M. Mumme K. Pelttari S. Gueven K. Nuss B. Von Rechenberg M. Jakob I. Martin A. Barbero

Summary

Nasal Chondrocytes are safe and feasible for tissue engineering approaches in articular cartilage repair.

Introduction

As compared to articular chondrocytes (AC), nasal septum chondrocytes (NC) proliferate faster and have a higher and more reproducible capacity to generate hyaline-like cartilaginous tissues. Moreover, the use of NC would allow reducing the morbidity associated with the harvesting of cartilage biopsy from the patient. The objective of the present study was to demonstrate safety and feasibility in the use of tissue engineered cartilage graft based on autologous nasal chondrocytes for the repair of articular defect in goats.


K. Herzog S. Durgam M. Stewart

Summary

Corticosteroids (CS) are commonly administered by intra-articular injection to control the symptoms of osteoarthritis; however, CSs also suppress articular chondrocyte matrix synthesis. Both triamcinolone and methylprednisolone acetate significantly suppressed BMPs −2 and −7, and TGF-b1 expression, suggesting a mechanism by which CSs suppress articular chondrocyte matrix synthesis and cartilage homeostasis.

Introduction

Osteoarthritis (OA) is a common and debilitating disease that affects approximately 30% of the US population and is also a major clinical problem in companion animals. There are many drugs available to manage the symptoms of OA. Of these, intra-articular corticosteroid (CS) administration is a common and very effective anti-arthritic therapy, and is frequently administered to equine athletes. CSs exert their potent anti-inflammatory effects by blocking phospholipase A and reducing inflammatory mediator production; however, CSs also suppress matrix-biosynthetic activity of articular chondrocytes. This activity, along with ther increased joint use that symptomatic relief allows, has been linked to ‘steroid arthropathy’; a progression of arthritis driven by compromised chondrocyte homeostatic capacity. Several lines of experimental and clinical evidence emphasise the importance of TGF-b and BMP autocrine/paracrine activity in maintaining the homeostatic status of articular chondrocytes (reviewed in Oshin and Stewart 2007). This study was carried out to address the following objectives: 1) To assess the effects of CS on expression of chondro-protective TGF-β and BMP ligands in equine articular chondrocytes, and 2) To determine if exogenous BMP ligand administration can mitigate the suppressive effects of CSs on articular chondrocyte synthesis of collagen type II (Coll II) and glycosaminoglycans (sGAG).


E. Hargrave-Thomas A. Thambyah S. McGlashan N. Broom

Summary

Macroscopic grading, histologic grading, morphometry, mineral analysis, and mechanical testing were performed to better understand the changes that occur in the cartilage, calcified cartilage, and subchondral bone in early osteoarthritis.

Introduction

The earliest changes in osteoarthritis (OA) remain poorly understood due to the difficulty in detecting OA before patients feel pain. We have published details of the mature bovine patella model showing the pre-OA state where no gross macroscopic changes are visible yet microstructural changes indicate very early degeneration. In this new study, we proceed to investigate this model further by more comprehensively quantifying the changes in articular cartilage (AC), zone of calcified cartilage (ZCC), and subchondral bone (SB) in pre and early OA.


R. Beckmann C. Hartz M. Tohidnezhad S. Neuss-Stein M. Ventura Ferreira B. Rath M. Tingart F. Pries D. Varoga T. Pufe

Aim of the study was to evaluate if abrasion-arthroplasty (AAP) and abrasion-chondroplasty (ACP) leads to a release of mesenchymal stem cell (MSC) like cells from the bone marrow to the joint cavity where they probably differentiate into a chondrogenic phenotype.

Introduction

Cartilage demage is a sever problem in our aging society. About 5 million people only in Germany are affected. Osteoathritis is a degeneration of cartilage caused by aging or traumata 50 % of the people over 40 have signs of osteoarthritis. But the ability of self-regeneration of cartilage is strongly limited. There are different approaches to therapy osteoathritic lesions. Arthroscopic treatment of OA includes bone marrow stimulation technique such as abrasion arthroplasty (AAP) and microfracturing (MF). Beside the support of chondrocyte progenitor cells the environment is also important for the commitment to chondrocytes. Therefore insulin-like growth factor-1 (IGF-1) and transforming growth factor beta-1 (TGF-β1) are important factors during the regeneration process. In the present study we characterised the heamarthrosis and the released cells after AAP and its ability to differentiate into the chondrocyte lineage.

Material and Methods

Postoperative haemarthrosis was taken 5, 22 or 44 hours after surgery. 7.5 mg Dexamethasone (Corticosteroid) was administered into the knee joint to prevent postoperative inflammation. Mononuclear cells were isolated from haemarthrosis from the drainage bottle by ficoll density gradient centrifugation. The isolated cells were characterised using fluorescence-activated cell-sorting (FACS) analysis for characteristic markers of MSC such as CD 44, 73, 90, 105. After expanding cells were cultured in a pellet culture. After 3 weeks, histochemistry and immunohistochemistry against Sox9, collagen II and proteoglycan were performed. The release of IGF1, BMP4 and BMP7 was analysed in haemarthrosis serum by ELISA and Luminex technology.


R. Olewinski M. Gupta M. Wimmer A. Hakimiyan A. Margulis L. Rappoport C. Pacione S. Chubinskaya

Summary

The ideal therapy for post-traumatic osteoarthritis (PTOA) must be mechanism-based and target multiple anabolic and catabolic pathways. Our results suggest an innovative combination of known pro-anabolic and anti-catabolic biologics to treat post-traumatic cartilage degeneration.

Introduction

Untreated joint injuries can result in cartilage wear and the development of PTOA. Previous studies identified the mechanisms that may govern the progression to PTOA. Here we hypothesised that targeted biologic interventions combined based on the type/time of cellular responses may constitute an effective novel treatment algorithm to arrest PTOA.


R. Sharma

For degenerative osteoarthritis of the knees, a variety of non-surgical management options have been tried from time to time. Medical management, chondroprotective agents, disease modifying drugs, viscosupplimentation etc. to name a few. Arthroscopic knee lavage with saline also has shown good results, with the effect of cleaning the debries from the joint.

Growth Factors Rich Plasma (GFRP) or Platelet Rich Plasma (PRP) is an emerging treatment therapy called “ Orthobiologics”. Alfa granules in platelets contain numerous growth factors which enhance tissue recovery dramatically by catalyzing the body's natural healing response. PRP also attracts Mesenchymal Stem Cells, which differentiate into variety of cell types during tissue repair processes & induce the production of new collagen by the fibroblasts, osteoblasts and chondrocytes as per the need of the parent tissue.

Knee lavage is done under local anesthesia using single antero-lateral portal. Four liters of saline is used to lavage the knee and at the end of procedure 80 mg. methyl prednisolone is injected. For GFRP injection, 100 cc of patient's blood is double centrifuged in the refrigerated blood component separator centrifuge in the blood bank giving about 15 cc of buffy layer having GFRP.

Since Feb. 2010, more than 1000 knees of different grades of osteoarthritis have been injected with GFRP and the results compared with other different treatment options. Results of few different combination therapies are presented in this study. 1. Knee Lavage Vs Autologous GFRP Injection (100+100 cases) 2. Knee Lavage + Autologous GFRP Injection in 1 knee Vs GFRP Injection only in other knee (200+200 Knees) 3. Visco-supplimentation Vs Autologous GFRP Injection. (10+10cases)

Results were analyzed up to 1 year as per VAS scale. Knee Lavage clears the joint of the microscopic and macroscopic debris of the cartilage and synovium which are causing chemical and mechanical irritation resulting in the inflammatory cascade. GFRP injection tries to repair the cartilage by the efficacy of the Growth factors contained therein. It has been observed that Knee Lavage and GFRP Injection have almost similar efficacy at 1 year, though knee lavage starts showing its effects early. GFRP therapy has shown better results compared to visco supplimentation at 1 year. Combination of knee lavage with GFRP injection showed much better results than GFRP injection alone and the results are inversely related to the grade of the osteoarthritis. Viscosupplimentation has very short lived efficacy.

It's concluded that Knee Lavage followed by GFRP injection gives the best long term results and this pilot project initiated, hopefully will go a long way in future to change the course of the management for osteoarthritis knees at a minimal cost and may obviate the need for Knee arthroplasty if started in early stages of Osteoartrhritis.


A. Abdulkarim N. Motterlini T.M. O'Donnell M.J. Neil

Summary Statement

This project proves that Patellofemoral (PF) joint degeneration is not a contraindication to medial unicompartmental knee replacement.

Introduction

Unicompartmental knee arthroplasty (UKA) is a recognised procedure for treatment of medial compartment osteoarthritis. Patellofemoral (PF) joint degeneration is widely considered to be a contraindication to medial unicompartmental knee replacement. We examined the validity of this preconception using information gathered prospectively on consecutive patients who underwent UKA using the Repicci II® UKA prosthesis for medial compartment osteoarthritis.


R. Senden I.C. Heyligers B. Grimm

Summary

Physical activity monitoring using a single accelerometer works reliably in clinical practice and is of added value as clinical outcome tool, as it provides objective and more precise information about a patient's activity compared to currently used questionnaires.

Introduction

Standard clinical outcome tools do not comply with the new generation of patients who are younger and more active. To capture the high functional demands of these patients, current outcome scales have been optimised (e.g. New-Knee Society Score: New-KSS), new outcome scales have been developed (e.g. Knee disability and Osteoarthritis Outcome score: KOOS). Also objective measurement tools (e.g. activity monitors) have become increasingly popular. This study evaluates the pre- and postoperative TKA status of patients using such optimised and new outcome tools.


B. Kerens B. Boonen M. Schotanus H. Lacroix P. Emans N. Kort

Summary Statement

This paper is the first to compare the results of unicompartmental to total knee arthroplasty revision surgery between cases with explained pain and cases with unexplained pain. Revision surgery for unexplained pain usually results in a less favourable outcome.

Introduction

Although it is suggested in literature that results of UKA to TKA revision surgery improve when the mechanism of failure is understood, a comparative study regarding this topic is lacking.


T.-W. Tai K.-A. Lai

Summary Statement

We present a simple and useful geometrical equation system to carry out the pre-operative planning and intra-operative assessments for total knee arthroplasty. These methods are extremely helpful in severely deformed lower limbs.

Introduction

Total knee arthroplasty is a highly successful surgery for most of the patients with knee osteoarthritis. With commercial instruments and jigs, most surgeons can correct the deformity and provided satisfactory results. However, in cases with severe extra-articular deformity, the instruments may mislead surgeons in making judgment of the true mechanical axis. We developed a geometrical equation system for pre-operative planning and intra-operative measurement to perform correct bony cuts and achieve good post-operative axis.


V. Moretti R. Shah

Summary Statement

Pulmonary embolism (PE) after total knee arthroplasty can have a significant impact on patient outcomes and healthcare costs. Efforts to prevent or minimise PE over the last 10 years have not had a significant impact on its occurrence at the national level.

Introduction

Pulmonary embolism (PE) is a rare but known potentially devastating complication of total knee arthroplasty (TKA). Significant healthcare resources and pharmaceutical research has been recently focused on preventing this complication but limited data exists regarding the early results of this great effort. The purpose of this study was to assess recent national trends in PE occurrence after TKA and evaluate patient outcomes related to this adverse event.


T. Onodera T. Yamashita N. Iwasaki F. Sasazawa

Summary Statement

The deletion of gangliosides enhanced OA development by elevating MMP-13 and ADAMTS-5 expression and accelerating chondrocyte apoptosis. Gangliosides possibly play suppressive roles in IL-1α-induced inflammatory signaling cascades.

Introduction

We have previously reported that glycosphingolipids (GSLs) play chondroprotective roles in the cartilage degradation process [1]. Gangliosides, one of the series of GSLs, are known to be important in intercellular signal transduction and cell-to-cell recognition [2]. Therefore, we hypothesised that gangliosides are important in cartilage metabolisms among the GSLs species. The purpose of this study was to determine the functional role of gangliosides in the development of OA in murine models.


F.-S. Wang L.-H. Wang J.-Y. Ko

Summary Statement

Increased Dkk-1 signaling is associated with OA occurrence and joint microenvironment damage. Interruption of Dkk1 action is beneficial to improve OA knees.

Introduction

Osteoarthritis (OA) is a leading cause of disability and healthcare financial burden for total knee arthroplasty, rehabilitation, and disability. Inappropriate mechanical stress, immunological, or biochemical regulation reportedly disturbs homeostasis among cartilage, synovium and subchondral bone microstructure that contributes to OA pathogenesis. Control of joint-deleterious factor action is an emerging strategy to ameliorate OA-induced joint deterioration. Dickkopf-1 (Dkk-1) is a potent inhibitor for Wnt/β-catenin signaling regulation of tissue development and remodeling in physiological or pathological contexts. Dkk-1 also acts as a master deleterious factor that represses osteoblast differentiation capacity and bone repair. Associations among Dkk-1 expression, chondrocyte fate, synovial fibroblast behavior or OA incidence are merit of characterization.


S. Snelling A. Price A. Carr L. Le I. Clark

Summary Statement

Dickkopf-3 is upregulated in OA cartilage and synovial tissue. In vitro studies show Dkk3 can prevent cartilage degradation and antagonise Wnt signaling. We hypothesis that Dkk3 can protect against OA-related cartilage destruction.

Introduction

Our group has previously shown that Dkk3, a member of the Dkk family of Wnt antagonists, is upregulated in OA cartilage and synovium. Levels of Dkk3 in synovial fluid are also increased in individuals with tricompartmental OA and after arthroscopy. The role of Dkk3 in cartilage or the factors regulating its expression are not currently understood. Correct regulation of cell signalling pathways is integral to cartilage homeostasis and thus the prevention of OA pathogenesis. Dkk3 is a member of the Dkk family of Wnt antagonists and therefore may impact on chondrocyte biology through interaction with the Wnt pathway. Dkk3 has also been found to influence TGFβ signalling in other cell systems.


G. Vadalà M. Musumeci A. Giacalone F. Russo V. Denaro

Summary Statement

Intra-articular injection of humanised monoclonal anti-VEGF antibody (Bevacizumab, Avastin®) in a osteoarthritis rabbit model is related to positive restorative effects in terms of histopathologic evaluation.

Introduction

Vascular endothelial growth factor (VEGF) is generally undetectable in adult human articular cartilage under physiological conditions. Upon exposure to pathological stimulation such as inflammation, hypoxia or accumulating mechanical stress, VEGF would be up regulated in hypertrophic chondrocytes of arthritic cartilage leading to osteophyte formation, disregulation of chondrocyte apoptosis and induction of catabolic factors, including matrix metalloproteinases (MMPs). This in vivo study aims to investigate the potential role of VEGF inhibition to treat Osteoarthritis (OA), through intra-articular injection of Bevacizumab, a humanised monoclonal anti-VEGF antibody, in a OA rabbit model.


H. Ito T. Fujii T. Kasahara M. Ishikawa M. Furu H. Shibuya S. Matsuda

Summary Statement

In articular cartilage defects, chemokines are upregulated and potentially induce the migration of bone marrow cells to accelerate the healing processes.

Introduction

The treatment of damaged articular cartilages is one of the most challenging issues in sports medicine and in aging societies. In the microfracture technique for the treatment of articular cartilage defects, bone marrow cells are assumed to migrate from the bone marrow. Bone marrow cells are well-known for playing crucial roles in the healing processes, but how they can migrate from underlying bone marrow remains to be investigated. We have previously shown that SDF-1, one of chemokines, play crucial roles in the recruitment of mesenchymal stem cells in bone healing processes, and the induction of SDF-1 can induce a successful bone repair. If the migration can be stimulated by any means in the cartilage defects, a better result can be expected. The aim of this study was to elucidate the mechanisms of the migration of bone marrow cells and which factors contribute to the processes.


Y. Sun A. Roberts N. Haines M. Ruffolo D. Mauerhan E. Hanley

Summary

PCA-III, a phosphocitrate analog, acts not only as a potent calcification inhibitor but also as a protective agent for extracellular matrices. PCA-III has potential as a disease-modifying drug in the treatment of primary osteoarthritis and posttraumatic osteoarthritis in humans.

Introduction

Phosphocitrate (PC) inhibits the development of primary osteoarthritis (OA) in Hartley guineas pigs but not menisectomy-induced OA in rabbits (1). We sought to examine the molecular mechanisms underlying the disease-modifying activity of PC, and evaluate the effect of PCA-III, a PC analog (PCA), on the development of primary and secondary OA.


A. Speirs A. Huang M. Lamontagne P. Beaule

Summary Statement

This study quantifies compositional differences in cartilage between CAM deformities of symptomatic FAI patients and normal cadaver controls. It shows a resemblance of CAM-FAI cartilage with those of osteoarthritic hips, objectively supporting previous hypothesis of abnormal contact stresses in CAM-FAI.

Introduction

Degeneration of cartilage within articular joints is a pathological feature of osteoarthritis (OA). Femoroacetabular impingement (FAI), a condition of abnormal contact between the articular surfaces of the femur and acetabulum, has been widely associated with early onset OA of the hip. The purpose of this study was to quantitatively compare the proteoglycan (PG) content of the weight-bearing cartilage in surgical FAI patients versus those of cadavers without FAI.


M. Armengol C.P. Brown P.A. Hulley A.J. Price H.S. Gill

Summary

The mechanical properties of porcine tibial plateau (TP) cartilage are shown to vary topographically. Low Elastic moduli (Em) were found in the positions where unicompartimental knee osteoarthritis (OA) lesions are typically expected to develop. These results suggest that there is a different response to load in these areas.

Introduction

OA is one of the ten most disabling diseases in developed countries. OA of the knee, in particular, is a major cause of mobility impairment; up to 40% of the population over the age of 70 suffers from OA of the knee. It has been observed that unicompartmental knee OA occurs with very distinct and repeatable lesion patterns. It is hypothesised that these patterns are the result of differences in the material properties throughout articular cartilage. The aim of this study was to measure the mechanical properties of porcine cartilage in a whole undamaged TP.


S. Ikemura T. Yamamoto G. Motomura R. Yamaguchi T. Mawatari Y. Iwamoto

Summary Statement

The incidence of osteonecrosis was significantly lower in the anti-vasospasm agent group (32%) than that in the control group (75%). Vasospasm is one of the important factors involved in the pathogenesis of steroid-induced osteonecrosis.

Introduction

A number of studies have suggested that ischemia is the principal pathomechanism of osteonecrosis, however, the detailed mechanism responsible for ischemia remains unclear. It has recently been reported that the Rho/Rho-kinase mediated pathway (Rho-kinase pathway) is considered to be involved in the possible pathogenesis of various cardiovascular disorders as well as cerebral vasospasm. We examined the effects of fasudil (Rho-kinase inhibitor), an anti-vasospasm agent, on the development of steroid-induced osteonecrosis in rabbits.


F.S. Wang R.-W. Wu

Summary Statement

Osteonecrosis of the femoral head (ONFH) is a multifactorial skeletal disorder. S100A9 represseses angiogenesis and vessel integrity in ONFH. It also may function as a marker of diagnosis in ONFH.

Introduction

Osteonecrosis of the femoral head (ONFH) is a multifactorial skeletal disorder characterised by ischemic deterioration, bone marrow edema and eventually femoral head collapse and joint destruction. Several surgical, pharmaceutical and non-invasive biophysical modalities have been employed to alleviate this joint disorder. Our proteomic analysis showed that ONFH patients displayed increased expression of S100A9 protein when compared with healthy volunteers. This study is designed to evaluate the pathogenesis of S100A9 on the patients of ONFH.


S. Semevolos M. Kinsley K. Duesterdieck-Zellmer

Summary Statement

Wnt/β-catenin gene expression is altered in early osteochondrosis, particularly in chondrocytes surrounding cartilage canals, and may be associated with disease initiation and/or pathogenesis.

Introduction

Osteochondrosis (OC) is a disease of articular cartilage development involving abnormal endochondral ossification along the osteochondral junction. Associated etiological factors of OC have included rapid growth rate, biomechanical trauma, abnormal collagen turnover, aberrant paracrine signaling, and altered blood supply involving cartilage canals. Wnt signaling regulates chondrocyte differentiation/maturation during pre-/post-natal cartilage development. Gene expression profiling of leukocytes has revealed aberrant expression of Wnt/β-catenin pathway in early OC. The objective of this study was to elucidate the expression of molecules associated with Wnt/β-catenin signaling in early OC using an equine model. Our hypothesis was that there would be increased expression of Wnt signaling molecules in chondrocytes adjacent to cartilage canals and the osteochondral junction in early OC lesions compared to normal controls.


S. Goel A.K. Singh K. Mohan A. Goel K.K. Gupta

Introduction

Very limited treatment options are available for osteoarthritis and most of them are for symptoms of osteoarthritis not for cause. Adult mesenchymal stem cells (MSCs), which have the ability to differentiate into cells of the chondrogenic lineage, have emerged as a candidate cell type with great potential for cell-based articular cartilage repair technologies. We conducted a study to see the effect of direct injection of stem cells on artificially created osteoarthritis model in rabbits.

Methods

Surgical instability was created in 20 adult white rabbits over 16 weeks old and weighing over 2 kg using a modification of the technique of Hulth et al. Only the right knees were operated (with other side serving as control). 12 weeks after surgery, X-rays were done for all 20 rabbits and confirmed for features of osteoarthritis like joint space narrowing, osteophyte formation etc. Bone marrow was aspirated and stem cells were prepared by method of Pittenger et al. Animals were divided into 2 groups of 10 each: Group I (with stem cell infusion) and Group II (control). The radiological evaluation was done at 12 week, 16 weeks, 20 weeks and histological evaluation at 16 and 20 weeks.


K. Hyodo T. Yoshioka H. Akaogi H. Sugaya K. Aoto H. Wada S. Sakai M. Yamazaki H. Mishima

Introduction

The goal of joint-preserving surgery for the treatment of osteonecrosis of the femoral head (ONFH) is to delay or prevent osteoarthritic development. Bone marrow is a source of osteogenic progenitors that are key elements in the process of bone formation and fracture healing. We established an easy-to-use method using a conventional manual blood bag centrifugation technique traditionally used for extracting buffy coats, for concentration of nucleated cells and platelets from clinical bone marrow aspirates to obtain osteogenic progenitors and growth factors. However, it is unclear whether the surgical goals are really achieved and if so in which patients. The purpose of this study was to identify demographic, clinical, and radiographic factors predicting total hip arthroplasty (THA) conversion after CABMAT for the treatment of idiopathic ONFH.

Methods

We retrospectively reviewed 123 patients (213 hips) who had CABMAT between 2003 and 2010. Sixty-five subjects (115 hips) were male and 58 (98 hips) were female with an average age at the time of CABMAT of 40.1 years. Of the 213 hips, 143 hips in 78 patients had corticosteroid-induced ONFH, 46 hips in 27 patients had alcohol-associated, and 24 hips in 18 patients had no etiological factors could be detected. The mean follow-up period was 60.5 months. The endpoint of evaluation was set as the time point which the patient required additional surgery (THA) depending on the spontaneous hip pain, x-ray change, and social back ground. The following factors were investigated: age, sex, body mass index (BMI), unilateral or bilateral, etiological factors, preoperative classification and staging, visual analogue scale (VAS), JOA clinical score. The 213 hips were divided into two groups: a THA conversion (THA) group and a non-THA conversion (non-THA) group. A multivariate analysis was performed using a logistic regression model.


S.Y. Lee E. Okumachi Y. Dogaki T. Niikura T. Iwakura T. Waki K. Nishida M. Kurosaka

Summary Statement

Low-intensity pulsed ultrasound (LIPUS) enhanced osteogenic differentiation of osteoprogenitor cells derived from mouse induced pluripotent cells (iPSCs) without embryoid body formation. Our findings provide insights on the development of LIPUS as an effective technology for bone regeneration strategies using iPSCs.

Introduction

iPSCs represent a promising cell source for regenerative medicine such as bone regeneration because of their unlimited self-renewal property and ability of differentiation into all somatic cell types. Recently, we developed an efficient protocol for generating a highly homogeneous population of osteoprogenitor cells from embryonic stem cells by using a direct-plating method without EB formation step. It is well-recognised that LIPUS accelerates the fracture healing. There have been several reports showing that LIPUS stimulates the osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro. To date, effect of LIPUS on iPSCs remains unknown. In this study, we investigated in vitro effect of LIPUS on osteogenic differentiation of osteoprogenitor cells derived from mouse iPS cells via a direct-plating method.


E. Ouellette S. Yang J. Morris A-L. Makowski W. Fung

Summary

Arthroscopic decompression of the lunate decreases clinical symptoms and slows progression of Kienböck's Disease.

Introduction

The purpose of this study was to investigate the outcomes of patients suffering from avascular necrosis of the lunate, or Kienböck's Disease, who received arthroscopic decompression to treat the ischemic lunate. Previous studies have demonstrated an elevated intraosseus pressure in the ischemic lunate, and it has been hypothesised that ischemia in the lunate is secondary to this elevated pressure and subsequent venous congestion, as opposed to diminished arterial supply. Based on this work we have used decompression of the lunate to prevent progression of the disease.


S. Oki N. Matsumura T. Morioka H. Ikegami Y. Kiriyama T. Nakamura Y. Toyama T. Nagura

Summary Statement

We measured scapulothoracic motions during humeral abduction with different humeral rotations in healthy subjects and whole cadaver models and clarified that humeral rotation significantly influenced scapular kinematics.

Introduction

Scapular dyskinesis has been observed in various shoulder disorders such as impingement syndrome or rotator cuff tears. However, the relationship between scapular kinematics and humeral positions remains unclear. We hypothesised that humeral rotation would influence scapular motions during humeral abduction and measured scapular motion relative to the thorax in the healthy subjects and whole cadavers.


M. Hamilton P. Diep C. Roche P.-H. Flurin T. Wright J. Zuckerman H. Routman

Summary Statement

Reverse shoulder design philosophy can impact external rotation moment arms. Lateralizing the humerus can increase the external rotator moment arms relative to normal anatomy.

Introduction

The design of reverse shoulders continues to evolve. These devices are unique in that they are not meant to reproduce the healthy anatomy. The reversal of the fulcurm in these devices impacts every muscle that surrounds the joint. This study is focused on analyzing the moment arms for the rotator cuff muscles involved in internal and external rotation for a number of reverse shoulder design philosophies.


K. Eraly D. Stoffelen N. Van Geel J. Demol P. Debeer

Summary Statement

In this study, excellent positioning of custom-made glenoid components was achieved using patient-specific guides. Achieving the preoperatively planned orientation of the component improved significantly and more screws were located inside the scapular bone compared to implantations without such guide.

Introduction

Today's techniques for total or reverse shoulder arthroplasty are limited when dealing with severe glenoid defects. The available procedures, for instance the use of bone allografts in combination with available standard implants, are technically difficult and tend to give uncertain outcomes (Hill et al. 2001; Elhassan et al. 2008; Sears et al. 2012). A durable fixation between bone and implant with optimal fit and implant positioning needs to be achieved. Custom-made defect-filling glenoid components are a new treatment option for severe glenoid defects. Despite that the patient-specific implants are uniquely designed to fit the patient's bone, it can be difficult to achieve the preoperatively planned position of the component, resulting in less optimal screw fixation. We hypothesised that the use of a patient-specific guide would improve implant and screw positioning. The aim of this study was to evaluate the added value of a newly developed patient-specific guide for implant and screw positioning, by comparing glenoid implantations with and without such guide.


S. Dun D. Warlop S. Swope

Summary Statement

The current biomecahnical study demonstrated that the stemless peripheral leg humeral component prototype and central screw humeral component prototype achieved similar initial fixation as stemmed Global Advantage humeral component in terms of resultant micromotion in total shoulder arthroplasty.

Introduction

A stemless humeral component may offer a variety of advantages over its stemmed counterpart, e.g. easier implantation, preservation of humeral bone stock, fewer humeral complications, etc. However, the initial fixation of a stemless humeral component typically depends on cementless metaphyseal press-fit, which could pose some challenges to the initial stability. Long-term success of cementless implants is highly related to osseous integration, which is affected by initial implant-bone interface motion1. The purpose of the study was to biomechanically compare micromotion at the implant-bone interface of three humeral components in total shoulder arthroplasty.


B. Dean R. Murphy K. Wheway B. Watkins S. Franklin K. Javaid A. Carr

Summary Statement

The peripheral neuronal phenotype is significantly altered in rotator cuff tendinopathy (RCT) with a clear upregulation of the Glutaminergic system being present in disease.

Introduction

Shoulder pain is the third most frequent cause of chronic musculoskeletal pain in the community and is usually caused by rotator cuff tendinopathy (RCT). The central and peripheral nervous system play an important role in both tissue homoeostasis and tendon healing. The Glutaminergic system is of key importance in driving the peripheral and central neuronal changes which increase the body's sensitivity to pain (1, 2). No study to date has investigated the role of the glutaminergic system in human RCT. We hypothesised that the peripheral neuronal phenotype would be altered in RCT, and would vary according to disease stage as measured by size of tear. The term ‘peripheral neuronal phenotype’ is used to refer to refer to specific characteristics of the peripheral nervous system, neuronal mediators and the receptors for these mediators in peripheral tissue


P. Ciampi C. Scotti G. Peretti M. Vitali G. Fraschini

Summary Statement

In this study, massive rotator cuff tears were treated using an absorbable collagen-based patch or a non-absorbable synthetic patch. Results demonstrated the efficacy of the use of the synthetic prolene patch especially for elderly patients

Introduction

The treatment of massive rotator cuff tears presents a challenging problem in shoulder surgery. Traditional repair techniques are associated with high rupture rates due to excessive tension on the repair and the presence of degenerated tendon tissue. These factors have led to attempts to reconstruct the rotator cuff with grafts, using synthetic materials or biologic tissues. The purpose of this study was to compare the efficacy of the use of pericardium patch with the use of prolene patch in the repair of extensive rotator cuff tears.


R. Holtby H. Razmjou G. Gunnis

Summary

In the sample studied, reparability of large and massive tears was associated with pre-op ASES and active external rotation in neutral position. Surgical factors affecting reparability were tear size, tendon mobility and shape of the tear.

Introduction

The limited literature has shown good results with partial repairs of large and massive tears of rotator cuff but the role of factors that affect reparability is less clear1–3. The purpose of this study was twofold, 1) to explore the predictive value of clinical and surgical factors on reparability of large and massive rotator cuff tears and 2) to examine the relationship between reparability and clinical and disability measures.