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View my account settingsThe Anterior Cruciate Ligament (ACL) plays a vital role in maintaining function and stability in the knee. Over the last several decades, much research has been focused on elucidating the anatomy, structural properties, biomechanics, pathology, and optimal treatments for the ACL. Through careful and objective study, the ACL can be understood to be a dynamic structure, rich in neurovascular supply. Although it is referred to as one ligament, it is comprised of two dis-tinct bundles which function synergistically to facilitate normal knee kinematics. The bony morphology of the knee defines normal knee kinematics, as well as the nature of the soft-tissue structures about the knee. Characterized by individual uniqueness, bony morphology varies from patient to patient. The ACL, which is a reflection of each patient's unique bony morphol-ogy, is inherently subject to both anatomic and morphologic variation as well. Furthermore, the ACL is subject to physiologic aging, which can affect the anatomic and structural properties of the ligament over time. A successful anatomic ACL Reconstruction, which may be considered the functional restoration of the ACL to its native dimensions, collagen orientation, and inser-tion sites according to individual anatomy, considers all these principles. It is vital to respect the nature we observe, rather than to “create” nature to fit a one-size-fits-all surgery. Double bundle ACL Reconstruction may therefore be thought of more as a concept rather than a specific technique, one that respects the individual unique anatomy of each patient to provide a truly indi-vidualized, anatomic, and value-based ACL Reconstruction.
Complex spinal deformities can cause pain, neurological symptoms and imbalance (sagittal and/or coronal), severely impairing patients’ quality of life and causing disability. Their treatment has always represented a tough challenge: prior to the introduction of modern internal fixation systems, the only option was an arthrodesis to prevent worsening of the deformity. Then, the introduction of pedicle screws allowed the surgeons to perform powerful corrective manoeuvres, distributing forces over multiple levels, to which eventually associate osteotomies. In treating flexible coronal deformities, in-ternal fixation and corrective manoeuvres may be sufficient: the combination of high density pedicle screws and direct vertebral rotation revolutionized surgical treatment of scoliosis.
However, spinal osteotomies are needed for correcting complex rigid deformities; the type of osteot-omy must be chosen according to the aetiology, type and apex of the deformity. When dealing with large radius deformities, spread over multiple levels and without fusion, multiple posterior column os-teotomies such as Smith-Petersen and Ponte (asymmetric, when treating scoliosis) can be performed, dissipating the correction over many levels. Conversely, the management of a sharp, angulated de-formity that involves a few vertebral levels and/or with bony fusion, requires more aggressive 3 col-umn osteotomies such as Pedicle Subtraction Osteotomies (PSO), Bone Disc Bone Osteotomies (BDBO) or Vertebral Column Resection (VCR). Sometimes the deformity is so severe that cannot be corrected with only one osteotomy: in this scenario, multilevel osteotomies can be performed.
The future of work brings several challenges and opportunities for occupational health and safety on three major drivers: the rapid progress of technological innovation; demographic changes, in particular ageing of the workforce and migration; and changes in the labour market, especially owing to new ways of per-forming jobs. Innovation technologies are leading to an overall transformation of industrial processes that offer huge developmental perspectives in the world of work and opportunities for society. In the field of prevention of musculoskeletal disorders, relevant progresses have been made in the clinical setting and in the context of care, also in relation to the ageing society. In the near future, the adaptation of workstations and the implementation of sensors and enabling technologies (collaborative robots and exoskeletons) will offer, together with the innovations in the clinic and orthopaedic surgery, a significant contribution to the reduction of risks from biomechanical overload, as well as support interventions to increase work ability and reduce the impact of disability. However, the potential risk scenarios for health and safety in the workplace, along with the progress in occupational health research, lead to the need for creating an inte-grated system of skills and approaches to adopt a Prevention through Design perspective. This requires designing and conceiving processes taking into consideration occupational risk prevention and guarantee-ing the return to work in a multidisciplinary and integrated perspective.
Cigarette smoking has a negative impact on the skeletal system by reducing bone mass and increasing the risk of fractures through its direct or indirect effects on bone remodeling. Recent evidence shows that smoking causes an imbalance in bone turnover, making bone vulnerable to osteoporosis and fragility fractures. In addition, cigarette smoking is known to have deleterious effects on fracture healing, as a positive correlation has been shown between the daily number of cigarettes smoked and years of exposure to smoking, although the underlying mechanisms are not fully understood. Smoking is also known to cause several medical and surgical complications responsible for longer hospital stays and a consequent increase in resource consumption. Smoking cessation is, therefore, highly advisable to prevent the onset of metabolic bone disease. However, some of the consequences appear to continue for decades. Based on this evidence, the aim of our work was to assess the impact of smoking on the skeletal system, particularly bone fractures, and to identify the pathophysiological mechanisms responsible for the impairment of fracture healing. Because smoking represents a major public health problem, understanding the association between cigarette smoking and the occurrence of bone disease is necessary in order to identify potential new targets for intervention.
Introduction and Objective
Nonunion is incomplete healing of fracture and fracture that lacks potential to heal without further intervention. Nonunion commonly presents with persistent pain, swelling, or instability. Those symptoms affect patient quality of life. It is known that using low intensity pulsed ultrasound (LIPUS) for fresh fractures promotes healing. However, effectiveness of LIPUS for nonunion is still controversial. If LIPUS is prove to be effective for healing nonunion, it can potentially provide an alternative to surgery. In addition, we can reduce costs by treating nonunion with LIPUS than performing revision surgery.
Materials and Methods
The two authors carried out a systematic search of PubMed, Ovid MEDLINE, and the Cochrane Library. Meta-analysis of healing rate in nonunion and delayed union patients who underwent LIPUS was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) instruction method using a random effects model.
Introduction and Objective
Despite the low incidence of pilon fractures among lower limb injuries, their high-impact nature presents difficulties in surgical management and recovery. Current literature includes a wide range of different management strategies, however there is no universal treatment algorithm. We aim to determine clinical outcomes in patients with open and closed pilon fractures, managed using a treatment algorithm that was applied consistently over the span of this study.
Materials and Methods
This retrospective study was conducted at a single institution, including 141 pilon fractures in 135 patients, from August 2014 to January 2021. AO/OTA classification was used to classify fractures. Among closed fractures, 12 had type 43A, 18 had type 43B, 61 had type 43C. Among open fractures, 11 had type 43A, 12 had type 43B, 27 had type 43C. Open fractures were further classified with Gustilo-Anderson (GA); type 1: n=8, type 2: n=10, type 3A: n=12, type 3B: n=20. Our treatment algorithm consisted of fine wire fixator (FWF) for severely comminuted closed fractures (AO/OTA type 43C3), or open fractures with severe soft tissue injury (GA type 3). Otherwise, open reduction internal fixation (ORIF) was performed. When required, minimally invasive osteosynthesis (MIO) was performed in combination with FWF to improve joint congruency. All open fractures, and closed fractures with severe soft tissue injury (skin contusion, fracture blister, severe oedema) were initially treated with temporary ankle-spanning external fixation. For all open fracture patients, surgical debridement, soft tissue cover with a free or pedicled flap were performed. For GA types 1 and 2, this was done with ORIF in the same operating session. Those with severe soft tissue injury (GA type 3) were treated with FWF four to six weeks after soft tissue management was completed. Primary outcome was AOFAS Ankle-Hindfoot score at 3, 6 and 12-months post-treatment. Secondary outcomes include time to partial weight-bear (PWB) and full weight-bear (FWB), bone union time. All complications were recorded.
Introduction and Objective
The early pro-inflammatory hematoma phase of bone healing is characterized by platelet activation followed by growth factor release. Bone marrow mesenchymal stromal cells (MSC) play a critical role in bone regeneration. However, the impact of the pro-inflammatory hematoma environment on the function of MSC is not fully understood. We here applied platelet-rich plasma (PRP) hydrogels to study how platelet-derived factors modulate functional properties of MSC in comparison to a non-inflammatory control environment simulated by fibrin (FBR) hydrogels.
Materials and Methods
MSC were isolated from acetabular bone marrow of patients undergoing hip arthroplasty. PRP was collected from pooled apheresis thrombocyte concentrates. The phenotype of MSC was analyzed after encapsulation in hydrogels or exposure with platelet-derived factors with regards to gene expression changes, cell viability, extracellular vesicle (EV) release and immunomodulatory effects utilizing cellular and molecular, flow cytometry, RT-PCR, western blot and immunofluorescence stainings.
Introduction and Objective
Ankle fractures are common and affect young adults as well as the elderly. An unstable ankle fracture treatment typically involves surgical fixation, immobilisation, and modified weight-bearing for six weeks. Non-weight bearing (NWB) cast immobilisation periods were used to protect the soft tissue envelope and osteosynthesis. This can have implications on patient function and may reduce independence, mobility and return to work. Newer trends in earlier mobilisation compete with traditional NWB doctrine, and weak consensus exists as to the best postoperative strategy. The purpose of this trial is to investigate the safety and efficacy of immediate weight-bearing (IWB) and range of motion (ROM) exercise regimes following ORIF of unstable ankle fractures with a particular focus on functional outcomes and complication rates.
Materials and Methods
A pragmatic randomised controlled multicentre trial, comparing IWB in a walking boot and ROM within 24 hours versus non-weight-bearing (NWB) and immobilisation in a cast for six weeks, following ORIF of all types of unstable adult ankle fractures (lateral malleolar, bimalleolar, trimalleolar with or without syndesmotic injury). The exclusion criteria are skeletal immaturity and tibial plafond fractures. The primary outcome measure is the functional Olerud-Molander Ankle Score (OMAS). Secondary outcomes include wound infection (deep and superficial), displacement of osteosynthesis, the full arc of ankle motion (plantar flexion and dorsal flection), RAND-36 Item Short Form Survey (SF-36) scoring, time to return to work and postoperative hospital length of stay.
Biomaterials are no longer considered innate structures and using functionalisation and biofabrication strategies to modulate a desired response whether it is a host or implant is currently an important focus in current research paradigms. Fundamentally, a thorough understanding of the host response will enable us to design appropriate strategies. The input from the host response needs to be weighed in depending on the host disease condition. Our current inputs have been through a thorough understanding of glyco-proteomics based tools which we are developing in our laboratory. In addition, biomaterials themselves provide immense therapeutic benefits which needs to be accounted in the design paradigm. Using functionalisation strategies such as enzymatic and hyperbranched linking systems, we have been able to link biomolecules to different structural moieties. The programmed assembly of biomolecules into higher-order self-organized systems is central to innumerable biological processes and development of the next generation of scaffolds. Recent design efforts have utilized a glycobiology and developmental biology approach toward both understanding and engineering supramolecular protein and sugar assemblies.
Introduction and Objective
Total joint replacement (TJR) is indicated for patients with end-stage osteoarthritis (OA) where conservative treatment has failed. Approximately 1.3 million primary hip replacement surgeries have been recorded in the United Kingdom since 2003 and this number is set to rise due to an increase in obesity as well as an ageing population. Total hip replacement (THR) has a survival rate of 85% at 20 years; the most common reason for failure is aseptic loosening which often occurs secondary to osteolysis caused by immune-mediated inflammation responses to wear debris generated from the materials used in the THR implant. Therefore, by understanding the biological steps by which biomaterials cause immune-mediated reactions it should be possible to prevent them in the future thereby reducing the number of costly revision surgeries required.
Materials and Methods
The human osteoblast-like cell line (MG-63) was seeded at a density of 100,000 cell per well of a 6-well plate and treated with and increasing doses (0.5, 5, and 50mm3 per cell) of cobalt-chromium (CoCr) particles generated on a six-station pin-on-plate wear generator or commercially available ceramic oxide nanopowders (Al2O3 and ZrO2) for 24 hours. TNF-alpha was used as a positive control and untreated cells as a negative control. Cells were then analysed by transmission electron microscopy (TEM) to determine whether the osteoblasts were capable of phagocytosing these biomaterials. MG-63 cells were used in conjunction with trypan blue and the XTT Cell Proliferation II Kit to assess cytotoxicity of the biomaterials investigated. Cells supernatants were also collected and analysed by enzyme-linked immunosorbant assay (ELISA) to investigate changes in pro-inflammatory protein secretion. Protein extracted from lysed cells was used for western blotting analysis to investigate RANKL protein expression to determine changes to osteolytic activation. Lysed cells were also used for RNA extraction and subsequent cDNA synthesis for real-time quantitative polymerase chain reaction (RT-qPCR) in order to assess changes to pro-inflammatory gene expression.
Introduction and Objective
Local cartilage defects in the knee are painful and mostly followed by arthritis. In order to avoid impaired mobility, the osteochondral defect might be bridged by a synthetic compound material: An osteoconductive titanium foam as an anchoring material in the subchondral bone and an infiltrated polymer as gliding material in contact with the surrounding natural cartilage.
Materials and Methods
Titanium foam cylinders (Ø38 mm) with porosities ranging from 57% to 77% were produced by powder metallurgy with two different grain sizes of the space holder (fine: 340 ± 110 μm, coarse: 530 ± 160 μm). The sintered titanium foam cylinders were infiltrated with UHMWPE powder on one end and UHMWPE bulk at the other end, at two different temperatures (160 °C, 200 °C), using a pressure of 20 MPa for 15 minutes. Smaller cylinders (Ø16 mm) were retrieved from the compound material by water jet cutting. The infiltration depths were determined by optical microscopy. The anchoring of the UHMWPE was measured by a shear test and the mechanical properties of the titanium foam were verified by a subsequent compression test. The tribological behaviour was investigated in protein containing liquid using fresh cartilage pins (Ø5 mm) sliding against a UHMWPE disc with or without a notch to simulate the gap between the implant and the surrounding cartilage. Friction coefficients were determined in a rotation tribometer and the cartilage wear in a multidirectional six-station tribometer from AMTI (load 10 – 50 N, sliding speed 20 mm/s, 37 °C).
Introduction and Objective
Total joint replacement is indicated for osteoarthritis where conservative treatment has failed, and in the UK the number of patients requiring hip and knee replacements is set to increase with an ageing population. Survival of total hip replacements is around 85% at 20 years with the most common reason for revision being aseptic loosening of the implant secondary to osteolysis, which is caused by immune-mediated reactions to implant debris. These debris can also cause pseudotumour formation. As revision surgery is associated with higher morbidity, mortality, infection rates, venous thromboembolism, resource demand and poorer subsequent function it is important to understand the mechanisms underlying the pro-inflammatory process to improve implant survival. Toll-like receptor 4 (TLR4), an innate immune receptor, has been demonstrated to mediate deleterious immune responses by the Tyson-Capper research group, including inflammatory cytokine interleukin-8 (IL-8) secretion. Statin use in epidemiological studies has been associated with reduced overall risk of revision surgery after hip replacement. In-vitro studies have demonstrated the potential for statins to reduce orthopaedic debris-induced immune responses which can lead to osteolysis and pseudotumour formation. As literature from cardiological investigations demonstrate that statins can reduce the expression and responsiveness of TLR4, this could be an exciting mechanism to exploit to reduce the host immune response to orthopaedic wear debris, thereby improving implant survival by reducing immune mediated osteolysis. This ongoing study investigates simvastatin's effect on cobalt ion-mediated changes in gene and protein expression of interleukin-8 and soluble-ICAM-1 (sICAM-1) which is an angiogenic factor implicated in pseudotumour formation.
Materials and Methods
TLR4-expressing human monocyte/macrophage THP-1 cells were pre-incubated with 50μM simvastatin for 2-hours or a vehicle control, before being exposed to exposed to 0.75mM cobalt chloride, in addition to a further 24-hour co-incubation with 50μM simvastatin or vehicle control. IL-8 protein and sICAM-1 secretion was measured by enzyme-linked immunosorbent assay (ELISA). Gene expression changes were quantified by TaqMan-based real time polymerase chain reaction.
Introduction and Objective
Alveolar bone resorption following tooth extraction or periodontal disease compromises the bone volume required to ensure the stability of an implant. Guided bone regeneration (GBR) is one of the most attractive technique for restoring oral bone defects, where an occlusive membrane is positioned over the bone graft material, providing space maintenance required to seclude soft tissue infiltration and to promote bone regeneration. However, bone regeneration is in many cases impeded by a lack of an adequate tissue vascularization and/or by bacterial contamination. Using simultaneous spray coating of interacting species (SSCIS) process, a bone inspired coating made of calcium phosphate-chitosan-hyaluronic acid was built on one side of a nanofibrous GBR collagen membrane in order to improve its biological properties.
Materials and Methods
First, the physicochemical characterizations of the resulting hybrid coating were performed by scanning electron microscopy, X-ray photoelectron, infrared spectroscopies and high-resolution transmission electron microscopy. Then human mesenchymal stem cells (MSCs) and human monocytes were cultured on those membranes. Biocompatibility and bioactivity of the hybrid coated membrane were respectively evaluated through MSCs proliferation (WST-1 and DNA quantification) and visualization; and cytokine release by MSCs and monocytes (ELISA and endothelial cells recruitment). Antibacterial properties of the hybrid coating were then tested against S. aureus and P. aeruginosa, and through MSCs/bacteria interactions. Finally, a preclinical in vivo study was conducted on rat calvaria bone defect. The newly formed bone was characterized 8 weeks post implantation through μCT reconstructions, histological characterizations (Masson's Trichrome and Von Kossa stain), immunohistochemistry analysis and second harmonic generation. Biomechanical features of newly formed bone were determined.
Introduction and Objective
In anticipation of reduced workload and need for minimisation of staff contact with infectious patients during the COVID-19 lockdown in 2020, Cairns Hospital reduced the junior orthopaedic staffing and absolved team structure.
Materials and Methods
We performed a retrospective audit of our department's workload during a predetermined three week period during the 2020 lockdown and in 2019.
Introduction and Objective
An important subset of patients is dissatisfied after total joint arthroplasty (TJA) due to residual functional impairment. This study investigated the assessment of objectively measured step-up performance following TJA, to identify patients with poor functional improvement after surgery, and to predict residual functional impairment during early postoperative rehabilitation. Secondary, longitudinal changes of block step-up (BS) transfers were compared with functional changes of subjective patient reported outcome measures (PROMs) following TJA.
Materials and Methods
Patients with end stage hip or knee osteoarthritis (n = 76, m/f = 44/32; mean age = 64.4 standard deviation 9.4 years) were measured preoperatively and 3 and 12 months postoperatively. PROMs were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function subscore. BS transfers were assessed by wearable-derived measures of time. In our cohort, subgroups were formed based on either 1) WOMAC function score or 2) BS performance, isolating the worst performing quartile (impaired) of each measure from the better performing others (non-impaired). Subgroup comparisons were performed with the Man-Whitney-U test and Wilcoxon Signed rank test resp. Responsiveness was calculated by the effect size, correlations with Pearson's correlation coefficient. A regression analysis was conducted to investigate predictors of poor functional outcome.
Introduction and Objective
Hip osteoarthritis (OA) is the leading cause for total hip arthroplasty (THA). Although, being considered as the surgery of the century up to 23% of the patients report long-term pain and deficits in physical function and muscle strength may persist after THA. Progressive resistance training (PRT) appear to improve several outcomes moderately in patients with hip OA. Current treatment selection is based on low-level evidence as no randomised controlled trials have compared THA to non-surgical treatment. The primary objective of this trial is to determine the effectiveness of THA followed by standard care compared to 12 weeks of supervised PRT followed by 12 weeks of optional unsupervised PRT, on changes in hip pain and function, in patients with severe hip OA after 6 months.
Materials and Methods
This is a protocol for a multicentre, parallel-group, assessor blinded, randomised controlled superiority trial. Patients aged ≥50 years with clinical and radiographic hip OA found eligible for THA by an orthopaedic surgeon will be randomised to THA or PRT (allocation 1:1). The primary outcome will be change in patient-reported hip pain and function, measured using the Oxford Hip Score. Key secondary outcomes will be change in the Hip disability and Osteoarthritis Outcome Score subscales, University of California Los Angeles Activity Score, 40-meter fast-paced walk test, 30-second chair stand test, and number of serious adverse events.
Introduction and Objective
Kinematic Alignment (KA) is a surgical technique that restores the native knee alignment following Total Knee Arthroplasty (TKA). The association of this technique with a medial pivot implant design (MP) attempts to reestablish the physiological kinematics of the knee. Aim of this study is to analyze the clinical and radiological outcomes of patients undergoing MP-TKA with kinematic alignment, and to assess the effect of the limb alignment and the orientation of the tibial component on the clinical outcomes.
Materials and Methods
We retrospectively analyzed 63 patients who underwent kinematic aligned medial pivot TKA from September 2018 to January 2020. Patient-Related Outcomes (PROMs) and radiological measures were collected at baseline, 3 months and 12 months after surgery.
Introduction and Objective
In recent years, along with the extending longevity of patients and the increase in their functional demands, the number of annually performed RSA and the incidence of complications are also increasing. When a complication occurs, the patient often needs multiple surgeries to restore the function of the upper limb. Revision implants are directly responsible for the critical reduction of the bone stock, especially in the shoulder. The purpose of this paper is to report the use of allograft bone to restore the bone stock of the glenoid in the treatment of an aseptic glenoid component loosening after a reverse shoulder arthroplasty (RSA).
Materials and Methods
An 86-years-old man came to our attention for aseptic glenoid component loosening after RSA. Plain radiographs showed a complete dislocation of the glenoid component with 2 broken screws in the neck of glenoid. CT scans confirmed the severe reduction of the glenoid bone stock and critical bone resorption and were used for the preoperative planning. To our opinion, given the critical bone defect, the only viable option was revision surgery with restoration of bone stock. We planned to use a bone graft harvested from distal bone bank femur as component augmentation. During the revision procedure the baseplate with a long central peg was implanted “on table” on the allograft and an appropriate osteotomy was made to customize the allograft on the glenoid defect according to the CT-based preoperative planning. The Bio-component was implanted with stable screws fixation on residual scapula. We decided not to replace the humeral component since it was stable and showed no signs of mobilization.
Introduction and Objective
Continuous peripheral nerve blocks (cPNBs) have shown good results in pain management after orthopedic surgeries. However, the variation of performance between different subspecialities is unknown. The aim of this study is to describe our experience with cPNBs after lower limb orthopedic surgeries in different subspecialties.
Materials and Methods
This prospective cohort study was performed on collected data from cPNBs after orthopedic surgeries in lower limbs. Catheters were placed by experienced anesthesiologists using sterile technique. After catheterization, the patients were examined daily, by specially educated acute pain service nurses. The characteristics of the patients, duration of catheterization, severity of the post-operative pain, need for additional opioids, and possible complications were registered.
Nonunions occur in situations with interrupted fracture healing process and indicate conditions where the fracture has no potential to heal without further intervention. Per definition, no healing is detected nine months post operation and there is no visible progress of healing over the last three months. The classification of nonunions as hypertrophic, oligotrophic, atrophic and pseudoarthosis, as well as aseptic or septic, identifies mechanical and biological requirements for fracture healing that have not been met. The overall treatment strategy comprises identification and elimination of the problems. However, current clinical methods to determine the state of healing are based on highly subjective radiographic evaluation or clinical examination.
A data collection telemetric system for objective continuous measurement of the load carried by a bridging smart implant was developed to assess the mechanical stability and monitor bone healing in complicated fracture situations. The first results from a clinical trial show that the system is capable to offer early warning of nonunions or poor fracture healing.
Nonunions are often multifactorial in nature and not just related to a biomechanical problem. Their successful treatment requires consideration of both biological and mechanical aspects. Disturbed vascularity and stability are the most important factors. Infection could be another complicating factor resulting in unpredictable long-time treatment. New technologies for monitoring of fracture healing in addition to radiographic evaluation and clinical examination seem to be promising for early detection of nonunions.
Introduction and Objective
Clinically, it is considered that spastic muscles of patients with cerebral palsy (CP) are shortened, and produce higher force in shorter muscle lengths. Yet, direct quantification of spastic muscles’ forces is rare. Remarkably, previous intraoperative tests in which muscle forces are measured directly as a function of joint angle showed for spastic gracilis (GRA) that its passive forces are low, and only a small percentage of its maximum active force is measured in flexed knee positions. However, the relationship of force characteristics of spastic GRA with its muscle-tendon unit length (lMTU) is unknown. Combining intraoperative experiments with participants’ musculoskeletal models developed based on their gait analyses, we aimed to test if spastic GRA muscle (1) operates at short lMTU compared to that of typically developing (TD) children, and exerts higher (2) passive and (3) active forces at shorter lengths, within gait-relevant lMTU range.
Materials and Methods
Ten limbs of seven children with CP (GMFCS-II) were tested. Pre-surgery, gait analyses were conducted. Intraoperatively, isometric spastic GRA distal forces were measured in ten hip-knee joint angle combinations, in two conditions: (i) passive state and (ii) maximal activation of the GRA exclusively. In OpenSim, gait_2392 model was used for each limb to calculate lMTU's per each hip and knee angle combination and the gait-relevant lMTU range, and to analyze gait relevant spastic muscle force - lMTU data. lMTU values were normalized for the participants’ thigh lengths. Two-way ANOVA was used to compare the patients’ lMTU to those of the seven age-matched TD children to test the first hypothesis. In order to test the second and the third hypotheses, Spearman's rank correlation coefficient (ρ) was calculated to seek a correlation between the muscle's operational length (represented by mean lMTU within gait cycle) and muscular force characteristics (the percent force at shortest lMTU of peak force, either in passive or in active conditions) within gait-relevant lMTU range.
Introduction and Objective
Medial Knee Osteoarthritis (MKO) is associated with abnormal knee varism, this resulting in altered locomotion and abnormal loading at tibio-femoral condylar contacts. To prevent end-stage MKO, medial compartment decompression is selectively considered and, when required, executed via High Tibial Osteotomy (HTO). This is expected to restore normal knee alignment, load distribution and locomotion. In biomechanics, HTO efficacy may be investigated by a thorough analysis of the ground reaction forces (GRF), whose orientation with respect to patient-specific knee morphology should reflect knee misalignment. Although multi-instrumental assessments are feasible, a customized combination of medical imaging and gait analysis (GA), including GRF data, rarely is considered. The aim of this study was to report an original methodology merging Computed-Tomography (CT) with GA and GFR data in order to depict a realistic patient-specific representation of the knee loading status during motion before and after HTO.
Materials and Methods
25 MKO-affected patients were selected for HTO. All patients received pre-operative clinical scoring, and radiological/instrumental assessments; so far, these were also executed post-operatively at 6-month follow-up on 7 of these patients. State-of-the-art GA was performed during walking and more demanding motor tasks, like squatting, stair-climbing/descending, and chair-rising/sitting. An 8-camera motion capture system, combined with wireless electromyography, and force platforms for GRF tracking, was used together with an own established protocol. This marker-set was enlarged with 4 additional skin-based non-collinear markers, attached around the tibial-plateau rim. While still wearing these markers, all analyzed patients received full lower-limb X-ray in standing posture a CT scan of the knee in weight-bearing Subsequently, relevant DICOMs were segmented to reconstruct the morphological models of the proximal tibia and the additional reference markers, for a robust anatomical reference frame to be defined on the tibia. These marker trajectories during motion were then registered to the corresponding from CT-based 3D reconstruction. Relevant registration matrices then were used to report GRF data on the reconstructed tibial model. Intersection paths of GRF vectors with respect to the tibial-plateau plane were calculated, together with their centroids.
Introduction and Objective
The human body is designed to walk in an efficient way. As energy can be stored in elastic structures, it is no surprise that the strongest elastic structure of the human body, the iliofemoral ligament (IFL), is located in the lower limb. Numerous popular surgical hip interventions, however, affect the structural integrity of the hip capsule and there is a growing evidence that surgical repair of the capsule improves the surgical outcome. Though, the exact contribution of the iliofemoral ligament in energy efficient hip function remains unelucidated. Therefore, the objective of this study was to evaluate the influence of the IFL on energy efficient ambulation.
Materials and Methods
In order to assess the potential passive contribution of the IFL to energy efficient ambulation, we simulated walking using the large public dataset (n=50) from Schreiber in a the AnyBody musculoskeletal modeling environment with and without the inclusion of the IFL. The work required from the psoas, iliacus, sartorius, quadriceps and gluteal muscles was evaluated in both situations. Considering the large uncertainty on ligament properties a parameter study was included.
Introduction and Objective
Plating of geriatric distal femoral fractures with Locking Compression Plate Distal Femur (LCP–DF) often requires augmentation with a supplemental medial plate to achieve sufficient stability allowing early mobilization. However, medial vital structures may be impaired by supplemental medial plating using a straight plate. Therefore, a helically shaped medial plate may be used to avoid damage of these structures. Aim of the current study was to investigate the biomechanical competence of augmented LCP–DF plating using a supplemental straight versus helically shaped medial plate.
Materials and Methods
Ten pairs of human cadaveric femora with poor bone quality were assigned pairwise for instrumentation using a lateral anatomical 15-hole LCP–DF combined with a medial 14-hole LCP, the latter being either straight or manually pre-contoured to a 90-degree helical shape. An unstable distal femoral fracture AO/OTA 33–A3 was simulated by means of osteotomies. All specimens were biomechanically tested under non-destructive quasi-static and destructive progressively increasing combined cyclic axial and torsional loading in internal rotation, with monitoring by means of optical motion tracking.
Introduction and Objective
Neoangiogenesis drives the replacement of mineralized cartilage by trabecular bone during bone growth regulated by molecules like e.g. VEGF, OPG and RANKL and the close interaction of progenitors of osteoblasts, chondrocytes, endothelial cells and osteoclasts/chondroclasts. The Heparan sulfate proteoglycan Syndecan-1 (Sdc-1) plays a role in the interaction between osteoclasts and osteoblasts and the development of blood vessels. As the processes of osteogenesis and angiogenesis are closely related to each other in bone, we expected Sdc-1 to have an influence on vessel structure during aging. Therefore, angiogenesis at the growth plate in mice of different ages was compared and the influence of Syndecan-1 deficiency was characterized.
Materials and Methods
Animals: C57BL/6 (WT) and Sdc1−/− mice were used for native bone analysis at 4, 12 and 18 month age. Femura were dissected, cryoprotected and embedded. Histology: Embedded bones were sectioned into 80um thick slices so that the 3D network of the vascularization of the bone could be visualized using an anti-Endomucin antibody and DAPI as counter staining. For semi-automatical quantification of the vessel bulbs we used a custom made software. In vitro angiogenesis: For aortic ring assay, aortic tissue was isolated from 4 month old mice, cut into 0.5mm rings and embedded in collagen type I matrix. Microvessel outgrowth was quantified after 6 days of culture.
Introduction and Objective
Traditionally, osteoarthritis (OA) has been associated mostly with degradation of cartilage only. More recently, it has been established that other joint tissues, in particular bone, are also centrally involved. However, the link between these two tissues remains unclear. This relationship is particularly evident in post-traumatic OA (PTOA), where bone marrow lesions (BMLs), as well as fluctuating levels of inflammation, are present long before cartilage degradation begins. The process of bone-cartilage crosstalk has been challenging to study due to its multi-tissue complexity. Thus, the use of explant model systems have been crucial in advancing our knowledge. Thus, we developed a novel patellar explant model, to study bone cartilage crosstalk, in particular related to subchondral bone damage, as an alternative to traditional femoral head explants or cylindrical core specimens. The commonly used osteochondral explant models are limited, for our application, since they involve bone damage during harvest. The specifics aim of this study was to validate this novel patellar explant model by using IL-1B to stimulate the inflammatory response and mechanical stimulation to determine the subsequent developments of PTOA.
Materials and Methods
Lewis rats (n=48) were used to obtain patellar and femoral head explants which were harvested under an institutional ethical approval license. Explants were maintained in high glucose media (containing supplements), under sterile culture conditions. Initially, we characterised undamaged patellar explants and compared them with the commonly used femoral head. First, tissue viability was assessed using an assay of metabolic activity and cell damage. Second, we created chemical and mechanical damage in the form of IL-1B treatment, and mechanical stimulation, to replicate damage. Standard biochemical assays, histological assays and microstructural assays were used to evaluate responses. For chemical damage, explants were exposed to 10ng/ml of IL-1B for 24 hours at 0, 1, 3 and 7 days after harvesting. For mechanical damage, tissues were exposed to mechanical compression at 0.5 Hz, 10 % strain for 10 cycles, for 7 days. Contralateral patellae served as controls. In both groups, sGAG, ADAMTS4, and MMP-13 were measured as an assessment of representative cartilage responses while ALP, TRAP and CTSK were assessed as a representative of bone responses. In addition to this, histomorphometric, and immunohistochemical, evaluations of each explant system were also carried out.
Introduction and Objective
Global prevalence of obesity has risen almost three-fold between 1975 and 2016. Alongside the more well-known health implications of obesity such as cardiovascular disease, cancer and type II diabetes, is the effect of male obesity on testosterone depletion and hypogonadism. Hypogonadism is a well-known contributor to the acceleration of bone loss during aging, and obesity is the single biggest risk factor for testosterone deficiency in men. Understanding the micro and macro structural changes to bone in response to testosterone depletion in combination with a high fat ‘Western’ diet, will advance our understanding of the relationship between obesity and bone metabolism. This study investigated the impact of surgically induced testosterone depletion and subsequent testosterone treatment upon bone remodelling in mice fed a high fat diet.
Materials and Methods
Male ApoE−/− mice were split into 3 groups at 7 weeks of age and fed a high fat diet: Sham surgery with placebo treatment, orchiectomy surgery with placebo treatment, and orchiectomy surgery with testosterone treatment. Surgeries were performed at 8 weeks of age, followed by fortnightly testosterone treatment via injection. Mice were sacrificed at 25 weeks of age. Tibiae were collected and scanned ex-vivo at 4.3μm on a SkyScan 1272 Micro-CT scanner (Bruker). Left tibiae were used for assessment of trabecular and cortical Volumes of Interest (VOIs) 0.2mm and 1.0mm respectively from the growth-plate bridge break. Tibiae were subsequently paraffin embedded and sectioned at 4μm prior to immunohistochemical evaluation of alkaline phosphatase.
Introduction and Objective
The osteocyte, recognized as a major orchestrator of osteoblast and osteoclast activity, is the most important key player during bone remodeling processes. Imbalances that occur during bone remodeling, caused by hormone perturbations or alterations in mechanical loading, can induce bone disease as osteoporosis. Due to limited understanding of the underlying mechanisms, current therapies for osteoporosis cannot adequately address this imbalance because current studies of osteocytes rely on conventional cell culture that cannot recapitulate local in vivo microenvironments for the lack of control of the spatial/temporal distribution of cells and biomolecules. Microfluidics is the science and technology of microscale fluid manipulating and sensing and can help fill this gap.
Materials and Methods
We used a microfluidic device to enable the culture of osteocyte-like cells (MLO-Y4 and MLO-A5) in a 3D fashion. Osteocytes were cultured in a perfused and 160 μm high channel and embedded in a bone-like extracellular matrix: osteocytes were embedded in a matrigel- and collagen-based hydrogel enriched with nanostructured hydroxypatite crystals (HA-NP) to mimic bone. To set up the best combination of matrigel enriched with Type I collagen we used fluorescent microspheres and confocal analysis. To evaluate the viability and the expression of osteocytic markers, we used live-dead assay amd immunofluorescent staining and confocal analysis combined with automated quantification. For mineralization, we performed alizarin red staining.
Introduction and Objective
Type 2 diabetes mellitus (T2DM), and the often concurrent obesity, causes metabolic changes that affect many organs and tissues, including bone. Despite a normal or even higher bone mineral density (BMD), T2DM has often been associated with a higher fracture risk, indicating a compromised bone quality. In this work, we use a novel congenic leptin receptor-deficient BioBreeding Diabetes Resistant rat (BBDR.cg.lepr.cp) to investigate the impact of T2DM and obesity on bone morphology and architecture at the microscale.
Materials and Methods
Two different anatomical locations, i.e., femur and cranium, were studied combining micro-computed X-ray tomography (micro-CT) with scanning electron microscopy (SEM). Micro-CT data were examined using advanced image analysis tools in three-dimensions (3D).
Introduction and Objective
Osteonecrosis of the femoral head (ONFH) is an evolving and disabling condition that often leads to subchondral collapse in late stages. It is the underlying diagnosis for approximately 3%–12% of total hip arthroplasties (THAs) and the most frequent aetiology for young patients undergoing THA. To date, the pathophysiological mechanisms underlying ONFH remain poorly understood. In this study, we investigated whether ONFH without an obvious etiological factor is related to impaired osteoblast activities, as compared to age-matched patients with primary OA.
Materials and Methods
We cultured osteoblasts isolated from trabecular bone explants taken from the femoral head of patients with ONFH and from intertrochanteric region of patients with ONFH or with OA and compared their in vitro mineralisation capacity and secretion of paracrine factors.
Osteoarthritis (OA) is a major global disease with increasing prevalence. It is one of the most significant causes of disability worldwide and represents a major burden in terms of healthcare delivery and impact on the quality of life of patients. It is a cause of severe chronic pain and has given rise to alarming levels of opioid use and addiction. Despite this prevalence, there are no disease-modifying treatments which delay or reverse the degrative changes within joints which are characteristics of the disease. All treatments are symptom-modifying with the exception of joint arthroplasty, which is currently the most common surgical procedure carried out in US hospitals. Several pharmaceutical and biological interventions have been tested in recent years, including metalloproteinase inhibitors, chondrogenic agents such as Kartogenin, IL-1 antagonists and monoclonal antibodies. So far, none of these has provided an effective disease-modifying treatment. Cellular therapies have a great deal of promise because of their anti-inflammatory and regenerative effects. Mesenchymal stromal cells (MSCs) have been widely studied as a treatment for OA in preclinical and clinical assessments with generally positive results. As the clinical testing of these cells proceeds serious questions emerge relating to the quality and consistency of the therapeutic product and the need for better standardisation with regard to, for example, the tissue source and expansion conditions. Of equal importance is the need for deeper insight into the therapeutic mechanism, specifically the activity and phenotype of cells transplanted to the OA environment, their fate and interaction with local cells.
Carpal tunnel syndrome (CTS) is the most common condition affecting the hand, with a prevalence of 2–3% in most populations, and a lifetime incidence over 10%. There is consensus that CTS results from increased pressure in the carpal tunnel, which eventually affects nerve function, but, aside from direct trauma and space occupying lesions, there is no consensus on what causes the pressure to rise. In the absence of an identifiable biological mechanism, the most common treatment involves surgical opening of the carpal tunnel. Recent data suggests that CTS patients demonstrate, in the carpal tunnel synovium and subsynovial connective tissue (SSCT), evidence of cellular senescence, with a senescence associated secretory phenotype (SASP). This finding suggests the potential for a biological treatment for CTS with senolytic drugs. This presentation will review the evidence for CTS as a disease of cellular senescence, and our preliminary data on the effects of senolytics, including in a relevant animal model of CTS and SSCT fibrosis.
Introduction and Objective
Tranexamic acid (TXA) is used across surgical specialties to reduce perioperative bleeding. It has been shown to be effective in trauma, spinal surgery, and lower limb arthroplasty. The aim of this study is to investigate the clinical effectiveness of TXA in all types of shoulder surgery on bleeding and non-bleeding related outcomes.
Materials and Methods
This study was registered prospectively on the PROSPERO database (ref: CRD42020185482). A systematic review and meta-analysis of randomised controlled trials (RCTs) investigating intra-operative use of TXA versus placebo in any type of surgery to the shoulder girdle. Electronic databases searched included MEDLINE, EMBASE, PsychINFO, and the Cochrane Library. Risk of bias within studies was assessed using the Cochrane risk of bias v2.0 tool and Jadad score. Certainty of findings were reported using the GRADE approach. The primary outcome was total blood loss. Secondary outcomes included patient reported outcome measures, adverse events, and rate of blood transfusion.
Introduction and Objective
Only few studies have investigated the outcome of exercises in patients with glenohumeral osteoarthritis (OA) or rotator cuff tear arthropathy (CTA), and furthermore often excluded patients with a severe degree of OA. Several studies including a Cochrane review have suggested the need for trials comparing shoulder arthroplasty to non-surgical treatments. Before initiation of such a trial, the feasibility of progressive shoulder exercises (PSE) in patients, who are eligible for shoulder arthroplasty should be investigated. The aim was to investigate whether 12 weeks of PSE is feasible in patients with OA or CTA eligible for shoulder arthroplasty. Moreover, to report changes in shoulder function and range of motion (ROM) following the exercise program.
Materials and Methods
Eighteen patients (11 women, 14 OA), mean age 70 years (range 57–80), performed 12 weeks of PSE with 1 weekly physiotherapist-supervised and 2 weekly home-based sessions. Feasibility was measured by drop-out rate, adverse events, pain and adherence to PSE. Patients completed Western Ontario Osteoarthritis of the Shoulder (WOOS) score and Disabilities of the Arm, Shoulder and Hand (DASH).
Introduction and Objective
There remains much debate regarding the optimal method for surgical management of patients with long head of biceps pathology. The aim of this study was to compare the outcomes of tenotomy versus tenodesis.
Materials and Methods
This systematic review and meta-analysis was registered on PROSPERO (ref: CRD42020198658). Electronic databases searched included EMBASE, Medline, PsycINFO, and Cochrane Library. Randomized controlled trials (RCTs) comparing tenotomy versus tenodesis were included. Risk of bias within studies was assessed using the Cochrane risk of bias v2.0 tool and the Jadad score. The primary outcome included patient reported functional outcome measures pooled using standardized mean difference (SMD) and a random effects model. Secondary outcome measures included visual analogue scale (VAS), rate of cosmetic deformity (Popeye sign), range of motion, operative time, and elbow flexion strength.
Introduction and Objective
Carpal tunnel syndrome (CTS) is a very common compressive neuropathy involving the median nerve. The typical symptoms are paraesthesia, dysesthesia and loss of strength; in severe case, this compression deteriorates the sensorimotor control of the hand and interferes with the adjustment of the forces at the level of the fingers, thus affecting the components that are the basis of dexterity and control of fine movements. For these reasons, the CTS has repercussions on various activities of daily life, including writing skills. Word processing via PC and mobile device (touch-typing) require a fine control of the hand-wrist movement and of the opposition of the thumb, while in handwriting, gripping and gripping movements are carried out in a protracted manner. In modern society, present skills play a role of fundamental importance from an educational, professional and social point of view.
The aim of the study is to describe the effects of carpal tunnel release (CTR) on handwriting and digital writing performance.
Materials and Methods
We recruited patients suffering from carpal tunnel syndrome (CTS) who were candidates for CTR surgery and collected clinical and demographic data, including age, occupation, duration of symptoms and electromyography outcomes. The first trial session was carried out before surgery and the subsequent ones at 1, 2, 3, 4, 8 and 12 weeks after the CTR. These trials involved copying a 500-character paragraph by handwriting, personal computer (PC) and mobile device, for which a dedicate Google Colab web page was computed. We used as parameters the speed, expressed in words per minute (wpm), and the accuracy of copying, which was measured in number of errors (en). Moreover in each session the patient filled in the QuickDASH (Disabilities of the Arm, Shoulder, and Hand) questionnaire. We used the one-way anova to evaluate the change in the three performances and in the QuickDASH score in follow-up sessions. We used the two-way anova to detect a possible interactions between speed improvement and groups of variables, namely gender, writing frequency, schooling, diabetes, dysthyroidism and metabolic syndrome.
In the last decades, significant effort has been attempted to salvage the meniscus following injury.
Basic science approaches to meniscus repair include procedures for both meniscus regeneration and meniscus healing. Regeneration of meniscal tissue focuses on filling a defect with reparative tissue, which resembles the native structure and function of the meniscus. Procedures for meniscus healing, on the other hand, aim to accomplish adhesion between the margins of a meniscal lesion, with no attempt to regenerate or replace meniscal tissue.
Regeneration studies of tissue to fill a defect in the meniscus have shown interesting results, but complete restoration of the native meniscus has not yet been accomplished.
Healing of a meniscal lesion has been investigated in different models although none has demonstrated reproducible healing. Therefore, different paths of investigation must be undertaken, and one of these may be the cell-therapy / tissue engineering approach.
In a study from our group, we showed the capacity of chondrocyte-seeded cartilaginous scaffold to repair a bucket-handle lesion of the knee meniscus orthotopically in a large animal study. Following studies were done in order to test the potential of other scaffolds and different cell sources for the repair of the meniscal tissue. We have also evaluated the role of hypoxia in meniscal development in vitro as basis for future research in this field, as hypoxia could be be considered as a promoter for meniscal cells maturation, and opens considerably opportunities in the field of meniscus tissue engineering.
Introduction
Current cell-based treatments and marrow stimulating techniques to repair articular cartilage defects are limited in restoring the tissue in its native composition. Despite progress in cartilage tissue engineering and chondrogenesis in vitro, the main limitation of this approach is the progression towards hypertrophy during prolonged culture in pellets or embedded in biomaterials. The objectives of this study were (A) to compare human bone marrow-derived mesenchymal stromal cells (hMSC) chondrogenesis and hypertrophy in pellet culture from single cells or cell spheroids and (B) to investigate the effect of tyramine-modified hyaluronic acid (THA) and collagen I (Col) content in composite hydrogels on the chondrogenesis and hypertrophy of encapsulated hMSC spheroids.
Materials and Methods
Pellet cultures were prepared either from hMSC single cells (250’000 cells/pellet) or hMSC spheroids (282 cells/spheroid) at the same final cell concentration (250’000 cells/pellet = 887 spheroids/pellet). The effect of polymer concentration on encapsulated hMSC spheroids (887 spheroids/hydrogel) was investigated in THA-Col hydrogels (50μl) at the following concentrations (THA-Col mg/ml): Group (1) 12.5–2.5, (2) 16.7–1.7, (3) 12.5–1.7, (4) 16.7–2.5 mg/ml. All samples were cultured for 21 days in standard chondrogenic differentiation medium containing 10ng/ml TGF-β1. Chondrogenic differentiation and hypertrophy of both pellet cultures and hMSCs spheroids encapsulated in THA-Col were analysed using gene expression analysis (Aggrecan (ACAN), COL1A1, COL2A1, COL10A1), dimethylmethylene-Blue assay to quantify glycosaminoglycans (GAGs) retained in the samples and (immuno-) histological staining (Safranin-O, collagen II, aggrecan) on day 1 and day 21 (n=3 donors).
Introduction and Objective
Regeneration of cartilage injuries is greatly limited. Therefore, cartilage injuries are often the starting point for later osteoarthritis. In the past, various bioactive glass (BG) scaffolds have been developed to promote bone healing. Due to the fact that they induce the deposition of hydroxyapatite (HA) -the main component of bone matrix, these BG types are not suitable for chondrogenesis. Hence, a novel BG (Car12N) lacking HA formation, was established. Since BG are generally brittle the combination with polymers is helpful to achieve suitable biomechanic stability. The aim of this interdisciplinary project was to investigate the effects of biodegradable polymer Poly(D,L-lactide-co-glycolide) (PLLA) infiltration into a Car12N scaffold for cartilage tissue engineering.
Materials and Methods
BG scaffolds were infiltrated with PLLA using phase separation within a solvent. Pure BG Car12N scaffolds served as control. To assess whether the polymer was homogeneously distributed the polymer to glass ratio and pore contents in the upper, middle and lower third of the scaffolds were examined by light microscopy. For a more precise characterization of the scaffold topology, the glass strut length, the glass strut diameter and the pore circumference were also measured. Leaching tests in 0.1M HCl solution over 8 days were used to allow a gel layer formation on the scaffolds surface. Non-leached and leached scaffolds were subjected to strength testing. Cytotoxicity of the scaffolds with and without polymer was tested according to standards. Scaffolds were colonized with 27.777.8 per cm3 primary porcine articular chondrocytes (pACs) or primary human mesenchymal stromal cells (hMSCs), respectively. After cultivation for up to 35 days, the vitality, quantitative DNA and sulfated glycosaminoglycan (sGAG) contents per scaffold were determined.
Introduction and Objective
The meniscus is composed of two distinct regions, a vascular outer zone and an avascular inner zone. Due to vascularization, tears within the vascular zone can be treated by suturing. However, tears in the avascular zone have a poor healing capacity and partial meniscectomy is used to prevent further pain, although this leads to early osteoarthritis. Previous studies have demonstrated that the vascular zone contains a progenitor population with multilineage differentiation potential. Isolation and propagation of these progenitors can be used to develop cell-based therapies for treating meniscal defects. In vivo, the meniscus resides under a low oxygen environment, also known as physioxia (2–7% oxygen) and previous work suggests that it promotes the meniscal phenotype. The objective of the study was to isolate progenitor populations from both meniscus regions and to examine their clonogenecity and differentiation potential under both hyperoxia (20% oxygen) and physioxia (2% oxygen). We hypothesize that physioxia will have a beneficial effect on colony formation and trilineage differentiation of meniscal cells.
Materials and Methods
Human meniscus (n =4; mean age: 64 + 6) tissue was split into vascular and avascular regions, finely cut into small pieces and then sequentially digested in pronase (70U/mL) and collagenase (200U/mL) at 370C. Avascular and vascular meniscus cells were counted and split equally for expansion under hyperoxia and physioxia at a seeding density of 5 × 103 cells/cm2. At passage 1, cells were seeded at 2, 5 and 20 cells/cm2 in 10cm dishes for observing colony formation using crystal violet assay. At passage 3, vascular and avascular meniscus cells were differentiated towards the chondrogenic, osteogenic and adipogenic lineage. Chondrogenesis was evaluated using DMMB staining for GAG deposition, osteogenesis was assessed using Alizarin Red staining for calcium deposition, whilst adipogenesis was observed using Oil-Red-O staining for fat droplets.
Introduction and Objective
Current cartilage repair strategies lack adequate tissue integration capacity and often present mechanical failure at the graft-to-host tissue junction. The design of multilayered osteochondral tissue engineering (TE) constructs is an attractive approach to overcome these problems. However, calcium ion-release from resorbable bone-replacement materials was suggested to compromise chondrogenic differentiation of adjacent cartilage tissue and it is unclear whether articular chondrocytes (AC) or mesenchymal stroma cells (MSC) are more sensitive to such conditions. Aim of the study was to compare how elevated calcium levels affect cartilage matrix production during re-differentiation of AC versus chondrogenic differentiation of MSC. The results of this study will help to identify the ideal cell source for growth of neocartilage adjacent to a calcified bone replacement material for design of multilayered osteochondral TE approaches.
Materials and Methods
Expanded human AC and MSC (6–12 donors per group) were seeded in collagen type I/III scaffolds and cultured under standard chondrogenic conditions at control (1.8mM) or elevated (8.0mM) CaCl2 for 35 days. Proteoglycan and collagen production were assessed via radiolabel-incorporation, ELISA, qPCR and Western blotting. Differences between groups or cell types were calculated using the non-parametric Wilcoxon or Mann-Whitney U test, respectively, with p < 0.05 considered significant.
Rotational laxity increases the risk of anterior cruciate ligament (ACL) injuries and residual rotational laxity can result in inferior surgical outcomes and risk of retears.
The dynamic rotatory knee stability can be assessed through manual examination, but it is limited to the surgeon's experience and it provides inaccurate measurements, highlighting the need for objective measurement of knee rotational laxity. The objective measurement of knee laxity can help to better identify patients that may benefit from conservative treatment or those that require surgical treatment with or without concomitant extra-articular procedures.
We rely in Porto Knee Testing Device (PKTD®) to accurately measure sagittal and rotatory laxity of the knee, either individually or in a combined fashion. The PKTD® is safe and can be used in combination with CT or MRI, which allows to assess both the “anatomy” and the “function” in the same examination. By this way, we may have a total ACL rupture and a stable knee not requiring surgery or, on the other hand, the same injury scenario but with an unstable knee that requires surgical intervention (with or without lateral extra-articular tenodesis). In cases of partial ACL tears, it may be possible to identify some ligamentous fibers that remain functional, where the conservative treatment or augmentation techniques can provide satisfactory results. It can also identify when a posteromedial or posterolateral instability is associated. The PKTD® can also be used to follow-up the laxity results of conservative and surgical procedures and contribute to the decision-making of return to sports.
Introduction and Objective
Forced external rotation is hypothesized as the key mechanism of syndesmotic ankle injuries. This complex trauma pattern ruptures the syndesmotic ligaments and induces a three-dimensional deviation from the normal distal tibiofibular joint configuration. However, current diagnostic imaging modalities are impeded by a two-dimensional assessment, without taking into account ligamentous stabilizers. Therefore, our aim is two-fold: (1) to construct an articulated statistical shape model of the normal ankle with inclusion of ligamentous morphometry and (2) to apply this model in the assessment of a clinical cohort of patients with syndesmotic ankle injuries.
Materials and Methods
Three-dimensional models of the distal tibiofibular joint were analyzed in asymptomatic controls (N= 76; Mean age 63 +/− 19 years), patients with syndesmotic ankle injury (N = 13; Mean age 35 +/− 15 years), and their healthy contralateral equivalent (N = 13). Subsequently, the statistical shape model was generated after aligning all ankles based on the distal tibia. The position of the syndesmotic ligaments was predicted based on previously validated iterative shortest path calculation methodology. Evaluation of the model was described by means of accuracy, compactness and generalization. Canonical Correlation Analysis was performed to assess the influence of syndesmotic lesions on the distal tibiofibular joint congruency.
Introduction and Objective
Objectives: To determine the effectiveness of LIA compared to ACB in providing pain relief and reducing opiates usage in hamstring graft ACL reconstructions.
Materials and Methods
In a consecutive series of hamstring graft ACL reconstructions, patients received three different regional and/or anaesthetic techniques for pain relief. Three groups were studied: group 1: general anaesthetic (GA)+ ACB (n=38); group 2: GA + ACB + LIA (n=31) and group 3: GA+LIA (n=36). ACB was given under ultrasound guidance. LIA involved infiltration at skin incision site, capsule, periosteum and in the hamstring harvest tunnel. Analgesic medications were similar between the three groups as per standard multimodal analgesia (MMA). Patients were similar in demographics distribution and surgical technique. The postoperative pain and total morphine requirements were evaluated and recorded. The postoperative pain was assessed using the visual analogue scores (VAS) at 0hrs, 2hrs, 4hrs, weight bearing (WB) and discharge (DC).
Introduction and Objective
Anterior cruciate ligament reconstruction (ACLR) with tendon autografts is the “gold standard” technique for surgical treatment of ACL injuries. Common tendon graft choices include patellar tendon (PT), semitendinosus/gracilis “hamstring” tendon (HT), or quadriceps tendon (QT). Healing of the graft after ACLR may be affected by graft type since the tissue is subjected to mechanical stresses during post-operative rehabilitation that play important roles in graft integration, remodeling and maturation. Abnormal mechanical loading can result in high inflammatory and degradative processes and altered extracellular matrix (ECM) synthesis and remodeling, potentially modifying tissue structure, composition, and function. Because of the importance of load and ligamentization for tendon autografts, this study was designed to compare the differential inflammatory and degradative metabolic responses to loading by three tendon types commonly used for autograft ACL reconstruction.
Materials and Methods
With IRB approval (IRB # 2009879) and informed patient consent, portions of 9 QT, 7 PT and 6 HT were recovered at the time of standard of care ACLR surgeries. Tissues were minced and digested in 0.2 mg/ml collagenase solution for two hours and were then cultured in 10% FBS at 5% CO2, 37°C, and 95% humidity. Once confluent, cells were plated in Collagen Type I-coated BioFlex® plates (1 × 105 cells/well) and cultured for 2 days prior to the application of strain. Then, media was changed to supplemented DMEM with 2% FBS for the application of strain. Fibroblasts were subjected to continuous mechanical stimulation (2-s strain and 10-s relaxation at a 0.5 Hz frequency) at three different elongation strains (mechanical stress deprivation-0%, physiologic strain-4%, and supraphysiological strain-10%)9 for 6 days using the Flexcell FX-4000T strain system. Media was tested for inflammatory biomarkers (PGE2, IL-8, Gro-α, and MCP-1) and degradation biomarkers (GAG content, MMP-1, MMP-2, MMP-3, TIMP-1, and TIMP-2). Significant (p<0.05) difference between graft sources were assessed with Kruskal-Wallis test and post-hoc analysis. Results are reported as median± interquartile range (IQR).
Introduction and Objective
Osteochondral allograft (OCA) transplants have been used clinically for more than 40 years as a surgical option for joint restoration, particularly for young and active patients. While immediate graft rejection responses have not been documented, it is believed that the host's immunological responses may directly impact OCA viability, incorporation, integrity, and survival, and therefore, it is of the utmost importance to further optimize OCA transplantation outcomes. The influences of sub-rejection immune responses on OCA transplantation failures have not been fully elucidated therefore aimed to further characterize cellular features of OCA failures using immunohistochemistry (IHC) in our continued hopes for the successful optimization of this valuable surgical procedure.
Materials and Methods
With IRB approval, osteochondral tissues that were resected from the knee, hip, and ankle of patients undergoing standard-of-care revision surgeries (N=23) to treat OCA failures and tissues from unused portions of OCAs (N=7) that would otherwise be discarded were recovered. Subjective histologic assessments were performed on hematoxylin and eosin-stained and toluidine blue-stained sections by a pathologist who was blinded to patient demographics, outcomes data, and tissue source. IHC for CD3, CD8, and CD20 were performed to further characterize the and allow for subjective assessment of relevant immune responses.
The human amniotic membrane (hAM), derived from the placenta, possesses a low (nay inexistant) immunogenicity and exerts an anti-inflammatory, anti-fibrotic, antimicrobial, antiviral and analgesic effect. It is a source of stem cells and growth factors promoting tissue regeneration. hAM acts as an anatomical barrier with adequate mechanical properties (permeability, stability, elasticity, flexibility, resorbability) preventing the proliferation of fibrous tissue and promoting early neovascularization of the surgical site. Cryopreservation and lyophilization, with sometimes additional decellularization process, are the main preservation methods for hAM storage.
We examined the use of hAM in orthopaedic and maxillofacial bone surgery, specially to shorten the induced membrane technique (Gindraux, 2017). We investigated the cell survival in cryopreserved hAM (Laurent, 2014) and the capacity of intact hAM of in vitro osteodifferentiation (Gualdi, 2019). We explored its in vivo osteogenic potential in an ectopic model (Laurent, 2017) and, with Inserm U1026 BioTis, in a calvarial defect (Fenelon, 2018). Still piloted by U1026, decellularization and/or lyophilization process were developed (Fenelon, 2019) and, processed hAM capacities was assessed for guided bone regeneration (Fenelon 2020) and induced membrane technique (Fenelon, 2021) in mice.
We reported a limited function of hAM for bone defect management. In this light, we recognized medication-related osteonecrosis of the jaw (MRONJ) as appropriate model of disease to evaluate hAM impact on both oral mucosa and bone healing. We treated height compassionate patients (stage II, III) with cryopreserved hAM. A multicentric randomized clinical study (PHRC-I 2020 funding) will be soon conducted in France (regulatory and ethical authorization in progress).
Introduction and Objective
In multiple trauma patients, as well as in the healing of isolated fractures (Fx) with heavy bleeding (trauma haemorrhage, TH), complications occur very often. This is particularly evident in elderly patients over 65 years of age. Since these accompanying circumstances strongly influence the clinical course of treatment, the influence of age on bone regeneration after femoral fracture and severe blood loss was investigated in this study.
Materials and Methods
12 young (17–26 weeks) and 12 old (64–72 weeks) male C57BL / 6J mice per group were examined. The fracture group Fx underwent an osteotomy after applying an external fixator. The THFx group also received blood pressure-controlled trauma hemorrhage (35 mmHg for 90 minutes) and reperfusion with Ringer's solution for 30 minutes. The Sham group received only the catheter and one external fixator. μCT scans of the femora were performed in vivo after 2 weeks and ex vivo after 3 weeks. Histological and biomechanical examinations were also carried out. The statistical significance was set at p ≤ 0.05. The non-normally distributed data were analyzed using the Mann-Whitney-U or Kruskal-Wallis test.
Introduction and Objective
It is widely accepted that interfragmentary strain stimulus promotes callus formation during secondary bone healing. However, the impact of the temporal variation of mechanical stimulation on fracture healing is still not well understood. Moreover, the minimum strain value that initiates callus formation is unknown. The goal of this study was to develop an active fixation system that allows for in vivo testing of varying temporal distribution of mechanical stimulation and that enables detection of the strain limit that initiates callus formation.
Materials and Methods
We employed a previously established wedge defect model at the sheep tibia. The model incorporates two partial osteotomies directed perpendicularly to each other, thus creating a bone fragment in the shape of a wedge. The defect was instrumented with an active fixator that tilts the wedge around its apex to create a gradient of interfragmentary strain along the cutting line. The active fixator was equipped with a force and displacement sensors to measure the stiffness of the repair tissue during the course of healing. We developed a controller that enabled programming of different stimulation protocols and their autonomous execution during the in vivo experiment. The system was implanted in two sheep for a period of five weeks. The device was configured to execute immediate stimulation for one animal (stimulation from Day 1), and delayed stimulation for the other (stimulation from Day 22). The daily stimulation protocol consisted of 1’000 loading events evenly distributed over 12 hours from 9:00 am to 9:00 pm. The healing progression was monitored by the in vivo stiffness measurements provided by the fixator and by weekly radiographs. The impact of the local strain magnitude on bone formation was qualitatively evaluated on a post-mortem high-resolution CT scan of the animal with immediate stimulation.
Introduction and Objective
Home-based monitoring of fracture healing has the potential of reducing routine follow-up and improve personalized fracture care. Implantable sensors measuring electrical impedance might detect changes in the electrical current as the fracture heals. The aim was to investigate whether electrical impedance correlated with radiographic fracture healing.
Materials and Methods
Eighteen rabbits were subjected to a tibial osteotomy that was stabilized with an external fixator. Two electrodes were positioned, one electrode placed within the medullary cavity and the other on the lateral cortex, both three millimeters from the osteotomy site. Transverse electrical impedance was measured daily across the fracture site at a frequency range of 5 Hz to 1 MHz using an Analog Discovery 2 Oscilloscope with Impedance Analyzer. Biweekly x-rays were taken and analyzed blinded using a modified anterior-posterior (AP) radiographic union score of the tibia (RUST). Each animal served as its own control by performing repeated measurements from time zero until the end of follow-up.
Introduction and Objective
Scaphoid waist fractures (SWF) are notable in upper limb trauma and predominantly occur in young men. Morbidities associated with SWF include fracture non-union, premature arthritis and humpback deformity. Delayed treatment and non-adherence to fracture immobilisation increases likelihood of these complications. There is evidence that men engage in negative health behaviours such as delayed help-seeking. The Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) conducted interviews in individuals who had sustained a SWF. Although SWIFFT showed multiple social determinants for the overall injury and healing experience, a key factor this novel study considers is age and sex. This study aimed to analyse interview data from young male participants in SWIFFT to help distinguish the experience of SWF in young men, through exploring the influence of masculinity.
Materials and Methods
A purposive sample of 12 young male participants were selected from SWIFFT. These participants were enrolled from a possibility of 13 different centres across Britain. There were 17 semi-structured interviews produced from these participants, and this was thought to be sufficient for data saturation. These interviews were evaluated through deductive thematic analysis with an open-coding approach, with respondents’ experiences being compared against themes documented in men's health literature. The “Braun and Clarke (2006) Six Phases of Thematic Analysis” methodology was adopted to perform this.
Chronic low back pain (cLBP) is a complex, multifaceted disorder where biological, psychological, and social factors affect its onset and trajectory. Consequently, cLBP encompasses many different disease variants, with multiple patient-specific mechanisms. The goal of NIH Back Pain Consortium (BACPAC) Research Program is to develop understanding of cLBP mechanisms and to develop algorithms that optimally match specific treatments to individual patients. To accomplish this, one research activity of BACPAC is to develop theoretical models for chronic low back pain based on the current state of knowledge in the scientific community, and to interrogate the relationships implied by the theoretical models using data generated by or available to BACPAC. The models consider biopsychosocial perspectives, and encompass both peripheral (i.e. low back) and central (i.e. spinal and supra-spinal) factors as well as proposed mechanisms of action of cLBP treatments. However, absent explanations, models/algorithms may fall short of regulatory requirements and clinician expectations, and ultimately may not be embraced by physicians and patients. To address this, BACPAC is developing a clinical utility roadmap (CUR) to clarify how models will be used in practice for selecting optimal treatments, monitoring response to treatment, and reducing health care utilization. This presentation will review the goals of BACPAC and how theoretical models and CUR are being used to support computational knowledge networks to integrate data from deeply phenotyped cLBP patients.
Introduction and Objective
After anterior cruciate ligament reconstruction one of the risk factors for graft (re-)rupture is an increased posterior tibial slope (PTS). The current treatment for PTS is a high tibial osteotomy (HTO). This is a free-hand method, with 1 degree of tibial slope correction considered to be equal to 1 or even 1.67 mm of the anterior wedge resection. Error rates in the frontal plane reported in literature vary from 1 – 8.6 degrees, and in the sagittal plane outcomes in a range of 2 – 8 degrees are reported when planned on PTSs of 3 – 5 degrees. Therefore, the free-hand method is considered to have limited accuracy. It is expected that HTO becomes more accurate with patient specific saw guides (PSGs), with an accuracy margin reported in literature of 2 degrees. This proof of concept porcine cadaver case study aimed to investigate whether the use of PSGs improves the accuracy of HTO to less than 2 degrees. Secondly, the reproducibility of tibial slope measurement was evaluated.
Materials and Methods
Preoperative MRI images of porcine cadaver knees (n = 3) were used to create 3D anatomical bone models (Mimics, Materialise, Belgium). These 3D models were subsequently used to develop PSGs (3-Matic, Materialise, Belgium) to correct all tibias for 3 degrees PTS and 4 degrees varus. The PSG mediated HTOs were performed by an experienced orthopaedic surgeon, after which postoperative MRI images were obtained. 3D anatomical models of postoperative tibias were created, and tibial slopes were assessed on both pre- and postoperative tibias. The tibial slope was defined as the angle between the mechanical axis and 3D tibial reference plane in the frontal and sagittal plane. The accuracy of the PSG mediated HTO (median and range) was defined as the difference in all possible combinations of the preoperatively planned and postoperatively obtained tibial slopes. To ensure reproducibility, the pre- and postoperative tibial slopes were measured thrice by one observer. The intra-class correlation coefficients (ICCs) were subsequently calculated to assess the intra-rater reliability (SPSS, IBM Corp., Armonk, N.Y., USA).
Introduction and Objective
The coronavirus (Covid-19) pandemic, first identified in China in December 2019, halted daily living with mandatory lockdowns imposed in Israel in March 2020. This halt induced a sedentary lifestyle for most citizens as well as a decreased physical activity time. These are both common risk factors for the development of low back pain (LBP) which is considered a major global medical and economical challenge effecting almost 1 in 3 people and a leading cause of Emergency Department (ED) visits. It is hypothesized that prevalence of minor LBP episodes during the first total lockdown should have increased compared to previous times. However, due to “Covid-19 fear” we expect a decrease in ED visits. We also speculate that rate of visits due to serious spinal illness (causing either immediate hospitalization or spinal surgery within 30-days of presentation) did not change.
Materials and Methods
Retrospective study based on patients visiting the ED in Tel Aviv Sourasky Medical Center During the first pandemic stage in 2020 compared to parallel periods in 2018 and 2019 due to LBP.
Introduction and Objective
Several studies have described double and triple femoral neck lengthening osteotomies to correct coxa brevis deformity, however, no overview exists in literature. Our aim was to perform the first systematic review of the outcomes of double and triple femoral neck lengthening.
Materials and Methods
After an extensive search in Pubmed, CINAHL and Embase libraries for published articles using the following search strategy: ‘(((proximal femoral deformity) OR hip dysplasia) OR coxa brevis) AND (((femoral neck lengthening) OR double proximal femoral osteotomy) OR triple proximal femoral osteotomy)’, we included studies reporting the results of double and triple femoral neck osteotomies. Clinical and radiological outcomes, and reported complications were extracted. The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Introduction and Objective
The effectiveness of anti-embolic graduated compression stockings (GCSs) has recently been questioned. The aim of this study is to systematically review all the relevant randomised controlled trials published to date.
Materials and Methods
We systematically reviewed all the randomised controlled trials comparing anti-embolism stockings with no stockings. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and CINAHL, Cochrane Musculoskeletal Injuries Group specialized register and the reference lists of articles as well as hand search results. Trials were independently assessed and data for the main outcome measures; deep vein thrombosis (DVT), pulmonary embolism and skin ulceration, were extracted by two reviewers.
Low back pain is thought to relate to intervertebral disc (IVD) degeneration. Although the mechanisms have not been clearly identified, exhaustion of nucleus pulposus cells and their producing matrix is regarded as one cause. The matrix of the IVD is continuously replenished and remodeled by tissue-specialized cells and are crucial in supporting the IVD function. However, due to aging, trauma, and genetic and lifestyle factors, the cells can lose their potency and viability, thereby limiting their collective matrix production capacity.
We have discovered the link between loss of angiopoietin-1 receptor (Tie2)-positive human NP progenitor cells (NPPC) and IVD degeneration. Tie2+ cells were characterized as undifferentiated cells with multipotency and possessing high self-renewal abilities. Thus we and others have proposed Tie2+ NPPC as a potent cell source for regenerative cell therapies against IVD degeneration. However, their utilization is hindered by low Tie2-expressing cell yields from NP tissue, in particular from commonly available older and degenerated tissue sources. Moreover, NPPC show a rapid Tie2 decrease due to cell differentiation as part of standard culture processes. As such, a need exists to optimize or develop new culture methods that enable the maintenance of Tie2-expressing NPPC. Trials to overcome these difficulties will be shared.
Introduction and Objective
Low back pain (LBP) is a major cause of long-term disability in adults worldwide and it is frequently attributed to intervertebral disc (IVD) degeneration. So far, no consensus has been reached regarding appropriate treatment and LBP management outcomes remain disappointing. Spine unloading or traction protocols are common non-surgical approaches to treat LBP. These treatments are widely used and result in pain relief, decreased disability or reduced need for surgery. However, the underlying mechanisms -namely, the IVD unloading mechanobiology- have not yet been studied. The aim of this first study was to assess the feasibility of IVD unloading in a large animal organ culture set-up and evaluate its impact on mechanobiology.
Materials and Methods
Bovine tail discs (diameter 16.1 mm ± 1.2 mm), including the endplates, were isolated and prepared for culture. Beside the day0 sample that was processed directly, three other discs were cultured for 3 days and processed on day4. One disc was loaded in the bioreactor according to a previously established physiological (compressive) loading protocol (2h/day, 0.2Hz). The two other discs were embedded in biocompatible resin, leaving the cartilage endplate free to permit nutrient diffusion, and fitted in the traction holder; one of these discs was kept in free swelling conditions, whereas the second was submitted to cyclic traction loading (2h/day, 0.2Hz) corresponding to 30% of the animal body weight corrected for organ culture.
Introduction and Objective
Intervertebral disc (IVD) degeneration accompanying with low back pain is a serious worldwide problem. Even though, surgical treatments are available for pain relief, there is an urgent need to establish enduring cell-based remedies. Notochordal (NC) cells as the ancestor of nucleus pulposus (NP) cells in human IVD are a promising therapeutic target. It has been reported that the loss of NC cells after childhood could promote the onset of disc degeneration. Thus, we firstly, aimed to optimise the culture of NC cells in vitro without using the FCS in alginate (3D) culture systems, secondly, investigate their behaviour in healthy and degenerate niche and lastly, co-culture these cells with degenerated NP cells to assess their regeneration potentials.
Materials and Methods
Porcine NC cells were extracted using pronase treatment followed by overnight digestion in 0.01% collagenase II. After extraction, cells were culture in 1.2% alginate beads (gold standard 3D culture) in either low glucose DMEM or αMEM medium. Cells were harvested after 24 hours, 1 week and 2 weeks for gene expression analysis and formalin fixed paraffin embedding. Quantitative Real-Time PCR and Immuno-staining were performed for analysis of NC markers (KRT18, FOXA2 and T) and COL I as a negative marker. Next, NC cells were cultured in healthy and degenerate medium to assess their viability and behaviour.
Introduction and Objective
Intervertebral disc (IVD) degeneration is one of the major contributors to low back pain, the leading cause of disability worldwide. This multifactorial pathological process involves the degradation of the extracellular matrix, inflammation, and cell loss due to apoptosis and senescence. While the deterioration of the extracellular matrix and cell loss lead to structural collapse of the IVD, increased levels of inflammation result in innervation and the development of pain. Amongst the known regulators of inflammation, toll-like receptors (TLRs) and more specifically TLR-2 have been shown to be specifically relevant in IVD degeneration. As strong post-transcriptional regulators, microRNAs (miRNAs) and their dysregulation has been connected to multiple pathologies, including degenerative diseases such as osteoarthritis and IVD degeneration. However, the role of miRNAs in TLR signalling in the IVD is still poorly understood and was hence investigated in this study.
Materials and Methods
Human Nucleus pulposus (hNP) and Annulus fibrosus (hAF) cells (n=5) were treated with the TLR-2/6 specific agonist PAM2CSK4 (100 ng/mL for 6 hours) in order to activate the TLR2 signalling pathway. After the activation both miRNA and mRNA were isolated, followed by next-generation sequencing and qPCR analysis of proinflammatory cytokines respectively. Furthermore, cell supernatants were used to analyze the secretion of proinflammatory cytokines with enzyme-linked immunosorbent assay. TLR-2 knockdown (siRNA) cells were used as a control. Statistical analysis was conducted by performing Kolmogorov-Smirnov test and a two-tailed Student's t-test using GraphPad Prism version 9.0.2 for Windows (GraphPad Software, La Jolla California USA).
Introduction and Objective
Low back pain (LBP) is a disorder strongly associated with intervertebral disc degeneration (IDD) with an important impact on the quality of life of affected people. To date, LBP treatment is based on conservative methods with the aim to reduce back pain without restoring the degenerative environment of the disc. The main cause of IDD is the drastic reduction of the proteoglycan content within the nucleus pulposus (NP), eventually leading to the loss of disc water content, micro-architecture, biochemical and mechanical properties. A promising approach for disc regeneration is represented by the transplantation of mesenchymal stromal cells (MSCs). The exact mechanism remains unknown. Growing evidence suggests that MSCs can influence cells and modulate cells’ behaviour by secreting a set of bioactive factors. MSCs secretome is composed of several molecules such as soluble protein, lipids, nucleic acids and extracellular vesicles (EVs) involved in inflammation, immunomodulation, cell survival and intercellular communication. The aim of this study was to evaluate the in vitro effects of MSCs secretome on human NP cells (hNPCs) in a 3D culture model with and without inflammatory stimulus.
Materials and Methods
MSCs secretome was collected from bone marrow-MSCs (BM-MSCs) and adipose tissue-MSCs (ASCs) after centrifugation and obtained by culturing cells without fetal bovine serum (FBS) for 48 hours. hNPCs were isolated from surgical specimens through digestion with type II collagenase, culture expanded in vitro, encapsulated in alginate beads (three-dimensional culture system) and treated with growth medium (controls), BM-MSCs or ASCs secretome with or without interleukin-1 beta (IL-1b). After 7 days, total RNA was extracted and reverse-transcribed. Gene expression levels of catabolic and anabolic genes were analyzed through real time-polymerase chain reaction (qPCR). Cell proliferation and glycosaminoglycan (GAG) production was assessed by flow cytometry and 1,9-dimethylmethylene blue (DMMB), respectively. hNPCs in alginate beads were stained with Live/Dead assay and detected using confocal immunofluorescence microscopy. Data were analyzed using Graphpad prism 8 and expressed as mean ± S.D. One-way ANOVA analysis was used to compare differences among the groups under exam.
Fragility fractures are skeletal complications associated with type 2 diabetes (T2D) causing disability, hospitalization, impaired quality of life, and increased mortality. Increased circulating sclerostin and accumulation of advanced glycation end-products (AGEs) are two potential mechanisms underlying low bone turnover and increased fracture risk. We have recently shown that T2D affects the expression of genes controlling bone formation (SOST and RUNX2) and that accumulation of AGEs is associated with impaired bone formation in T2D. We hypothesized that Wnt/B- catenin target genes are down-regulated in bone of T2D subjects as a consequence of decreased SOST and AGEs accumulation. To this end, we studied gene expression in extracts of bone samples obtained from femoral heads of 14 subjects with relatively well-controlled T2D (HbA1c 6.5±1.7%) and 21 control, non-diabetic postmenopausal women (age >65 years) undergoing hip replacement. There were no differences in age (73.2± .8 vs. 75.2±8.5 years) or BMI (27.7±5.6 vs. 29.9±5.4 kg/m2) between control and T2D groups, respectively. Expression of LEF1 mRNA was significantly lower in T2D compared to non-diabetic subjects (p=0.002), while DKK1 was not different between groups (p=0.108). Correlation analysis showed that DKK1 (r2=0.038; p=0.043) and HbA1c (r2=0.503; p=0.048) increased with age in T2D. COL1A1 mRNA trended lower in T2D compared to controls (p=0.056). Bone volume (9,333 ± 1,443 vs. 15,53 ± 2,442 mm2; p=0.048), mineralized volume (9,278 ± 1,418 vs. 15,45 ± 2,444 mm2; p=0.048) and BV/TV (0,2125 ± 0,03114 vs. 0,3719 ± 0,03196 %; p=0.002) measured by bone histomorphometry were lower in T2D compared to controls. Our data show that even in patients with relatively good glycemic control, T2D decreases expression of Wnt/B-catenin target genes andCOL1A1, associated with decreased bone density. These results may help understand the mechanisms underlying bone fragility in T2D.
Introduction and Objective
Malunion after trauma can lead to coronal plane malalignment in the lower limb. The mechanical hypothesis suggests that this alters the load distribution in the knee joint and that that this increased load may predispose to compartmental arthritis. This is generally accepted in the orthopaedic community and serves as the basis guiding deformity correction after malunion as well as congenital or insidious onset malalignment. Much of the literature surrounding the contribution of lower limb alignment to arthritis comes from cohort studies of incident osteoarthritis. There has been a causation dilemma perpetuated in a number of studies - suggesting malalignment does not contribute to, but is instead a consequence of, compartmental arthritis. In this investigation the relationship between compartmental (medial or lateral) arthritis and coronal plane malalignment (varus or valgus) in patients with post traumatic unilateral limb deformity was examined. This represents a specific niche cohort of patients in which worsened compartmental knee arthritis after extra-articular injury must rationally be attributed to malalignment.
Materials and Methods
The picture archiving system was searched to identify all 1160 long leg x ray films available at a major metropolitan trauma center over a 12-year period. Images were screened for inclusion and exclusion criteria, namely patients >10 years after traumatic long bone fracture without contralateral injury or arthroplasty to give 39 cases. Alignment was measured according to established surgical standards on long leg films by 3 independent reviewers, and arthritis scores Osteoarthritis Research Society International (OARSI) and Kellegren-Lawrence (KL) were recorded independently for each compartment of both knees. Malalignment was defined conservatively as mechanical axis deviation outside of 0–20 mm medial from centre of the knee, to give 27 patients. Comparison of mean compartmental arthritis score was performed for patients with varus and valgus malalignment, using Analysis of Variance and linear regression.
Introduction and Objective
Postoperative management regimes vary following open reduction and internal fixation of unstable ankle fractures. There is an evolving understanding that poorer outcomes could be associated with non-weight bearing protocols and immobilisation. Traditional non-weight bearing cast immobilisation may prevent loss of fixation, and this practice continues in many centres. The aim of this systematic review and meta-analysis is to compare the complication rate and functional outcomes of early weight-bearing (EWB) versus late weight-bearing (LWB) following open reduction and internal fixation of ankle fractures.
Materials and Methods
We performed a systematic review with a meta-analysis of controlled trials and comparative cohort studies. MEDLINE (via PubMed), Embase and the Cochrane Library electronic databases were searched inclusive of all date up to the search time. We included all studies that investigated the effect of weight-bearing following adults ankle fracture fixation by any means. All ankle fracture types, including isolated lateral malleolus fractures, isolated medial malleolus fractures, bi-malleolar fractures, tri-malleolar fractures and Syndesmosis injuries, were included. All weight-bearing protocols were considered in this review, i.e. immediate weight-bearing (IMW) within 24 hours of surgery, early weight-bearing (EWB) within three weeks of surgery, non-weight-bearing for 4 to 6 weeks from the surgery date (or late weight-bearing LWB). Studies that investigated mobilisation but not weight-bearing, non-English language publications and tibial Plafond fractures were excluded from this systematic review. We assessed the risk of bias using ROB 2 tools for randomised controlled trials and ROBINS-1 for cohort studies. Data extraction was performed using Covidence online software and meta-analysis by using RevMan 5.3.
Introduction and Objective
Dislocation of a hip hemiarthroplasty is a significant complication with a high mortality rate in elderly patients. Previous studies have shown a higher risk of dislocation in patients with neuromuscular conditions. In this study, we reviewed our larger cohort of patients to identify if there is a link between neuromuscular disorders and dislocation of hip hemiarthroplasty in patients with neuromuscular conditions.
Materials and Methods
We have retrospectively analysed a single-centre data that was collected over 34 years for patients with intracapsular neck of femur fracture who underwent hip hemiarthroplasty. The study population was composed of four groups: patients with no neuromuscular disorders, patients with Parkinson's disease, patients with previous stroke, and patients with mental impairment.
Introduction and Objective
Hemorrhagic shock and fractures are the most common injuries within multiple injured patients, inducing systemic and local inflammation in NF-kappaB-dependent manner. Alcohol intoxication, showing a high incidence with severe injuries, has immunomodulatory properties and implicates NF-kappaB downregulation. However, the mechanism is largely unknown. A20 deubiquitinase is a critical negative regulator of NF-kappaB activity and inflammation. Here, we investigate the role of A20 as a modifier of NF-kappaB-driven inflammation and remote lung injury in severely injured and alcohol-intoxicated mice.
Materials and Methods
Mice were randomly divided into four groups. Either sodium chloride or ethanol (35%, EtOH) was administrated by intragastral gavage one hour before trauma induction. In the trauma group, the animals underwent an osteotomy with external fracture fixation (Fx) followed by a pressure-controlled hemorrhagic shock (35±5 mmHg; 90 minutes) with subsequent resuscitation (H/R). Sham-operated animals underwent only surgical procedures. Mice were sacrificed at 24 hours. Fatty vacuoles and thus, the alcohol intoxication were evaluated by Oil red O staining of the liver. To assess the lung injury, hematoxylin eosin staining, determination of total protein concentration in bronchoalveolar lavage (BALF) and calculation of the lung injury score (LIS) were performed. Lungs were stained for neutrophil elastase, CXCL1 and active caspase-3 to determine neutrophil invasion, pro-inflammatory changes and apoptosis, respectively. The expression level of A20 was evaluated by immunofluorescence microscopy.
The medial opening-wedge high tibial osteotomy (OW-HTO) is an accepted option to treat the isolated medial compartment osteoarthritis (OA) in varus knee. Despite satisfactory outcomes were described in literature, consistent complication rate has been reported and the provided accuracy of coronal alignment correction using conventional HTO techniques falls short.
Patient specific instrumentations has been introduced with the aim to reduce complications and to improve the intra-operative accuracy according to the pre-operative plan, which is responsible for the clinical result of the surgery.
In this talk, an overview of the clinical results of HTO patient specific instrumentation available in literature will be performed.
Moreover, preliminary intra-operative and clinical results of a new customised 3-D printed cutting guide and fixation plate for OW-HTO will be presented.
Introduction and Objective
Individuals with type 2 diabetes (T2D) have a 3-fold increased risk of bone fracture compared to non-diabetics, with the majority of fractures occurring in the hip, vertebrae and wrists. However, unlike osteoporosis, in T2D, increased bone fragility is generally not accompanied by a reduction in bone mineral density (BMD). This implies that T2D is explained by poorer bone quality, whereby the intrinsic properties of the bone tissue itself are impaired, rather than bone mass. Yet, the mechanics remain unclear. The objective of this study is to (1) assess the fracture mechanics of bone at the structural and tissue level; and (2) investigate for changes in the composition of bone tissue along with measuring total fluorescent advanced glycation end products (fAGEs) from the skin, as T2D progresses with age in Zucker diabetic fatty (ZDF (fa/fa)) and lean Zucker (ZL (fa/+)) rats.
Materials and Methods
Right ulnae and skin sections were harvested from ZDF (fa/fa) (T2D) and ZL (fa/+) (Control) rats at 12 and 46 weeks (wks) of age (n = 8, per strain and age) and frozen. Right ulnae were thawed for 12 hrs before micro-CT (μCT) scanning to assess the microstructure and measure BMD. After scanning, ulnae were loaded until failure via three-point bending. Fourier transform-infrared microspectroscopy (FTIR) was used to measure various bone mineral- and collagen-related parameters such as, mineral-to-matrix ratio and nonenzymatic cross-link ratio. Finally, fAGEs were measured from skin sections using fluorescence spectrometry and an absorbance assay, reported in units of ng quinine/ mg collagen.
Introduction and Objective
Distal femoral fractures are commonly treated with a straight plate fixed to the lateral aspects of both proximal and distal fragments. However, the lateral approach may not always be desirable due to persisting soft-tissue or additional vascular injury necessitating a medial approach. These problems may be overcome by pre-contouring the plate in helically shaped fashion, allowing its distal part to be fixed to the medial aspect of the femoral condyle. The objective of this study was to investigate the biomechanical competence of medial femoral helical plating versus conventional straight lateral plating in an artificial distal femoral fracture model.
Materials and Methods
Twelve left artificial femora were instrumented with a 15-hole Locking Compression Plate – Distal Femur (LCP-DF) plate, using either conventional lateral plating technique with the plate left non-contoured, or the medial helical plating technique by pre-contouring the plate to a 180° helical shape and fixing its distal end to the medial femoral condyle (n=6). An unstable extraarticular distal femoral fracture was subsequently simulated by means of an osteotomy gap. All specimens were tested under quasi-static and progressively increasing cyclic axial und torsional loading until failure. Interfragmentary movements were monitored by means of optical motion tracking.
Introduction and Objective
Scapholunate instability is the most common cause of carpal instability. When this instability is left untreated, the mechanical relationship between the carpal bones is permanently disrupted, resulting in progressive degenerative changes in the radiocarpal and midcarpal joints. Different tenodesis methods are used in the treatment of acute or early chronic reducible scapholunate instability, where arthritis has not developed yet and the scapholunate ligament cannot be repaired. Although it has been reported that pain is reduced in the early follow up in clinical studies with these methods, radiological results differ between studies. The deterioration of these radiological parameters is associated with wrist osteoarthritis as previously stated. Therefore, more studies are needed to determine the tenodesis method that will improve the wrist biomechanics better and will last longer. In our study, two new tenodesis methods, spiral antipronation tenodesis, and anatomic front and back reconstruction (ANAFAB) were radiologically compared with triple ligament tenodesis (TLT), in the cadaver wrists.
Materials and Methods
The study was carried out on a total of 16 fresh frozen cadaver wrists. Samples were randomly allocated to the groups treated with 3 different scapholunate instability treatment methods. These are TLT (n: 6), spiral antipronation tenodesis (n: 5) and ANAFAB tenodesis (n: 5) groups. In all samples SLIL, DCSS, STT, DIC, RSC and LRL ligaments were cut in the same way to create scapholunate instability. Wrist CT scans were taken on the samples in 4 different states, in intact, after the ligaments were cut, after the reconstruction and after the movement cycle. In all of these 4 states, wrist CTs were taken in 6 different wrist positions. For every state and every position through tomography images; Scapholunate (SL) distance, Scapholunate (SL) angle, Radioscaphoid (RS) angle, Radiolunate (RL) angle, Capitolunate (CL) angle, Dorsal scaphoid translation (Dt) measurements were made.
Introduction and Objective
The geometry of the proximal tibia and distal femur is intimately linked with the biomechanics of the knee and it is to be considered in total knee arthroplasty (TKA) component positioning. The aim of the present study was to evaluate the proximal tibial torsion in relation to the flexion-extension axis of the knee in healthy and pathological cohort affected by knee osteoarthritis (OA).
Materials and Methods
We retrospectively analyzed computed tomography scans of OA knee of 59 patients prior to TKA and non-arthritic knee of 39 patients as control. Posterior condylar angle (PCA), femoral tibial torsion (TEAs-PTC and TEAs-PTT), proximal tibial torsion (PTC-PTT and PCAx-PTC) and distance between tibial tuberosity and the trochlear groove (TT-TG) were measured.
Hyaluronic acid (HA) is responsible for the viscoelastic properties of synovial fluid and cartilage. Compared to healthy joints, synovial fluid in osteoarthritic joints contains HA of lower concentration and molecular weight. Hyaluronic acid hybrid complexes are composed by long and short HA chains linked by H bonds. These rheological characteristics and viscoelastic properties were produced by thermal patented process without chemical modification. Chondroitin sulfate (CS) is one of the essential components of the articular cartilage matrix and plays a key role in cartilage's mechanical and elastic properties. Biotechnological chondroitin (CB) is produced through fermentative/biotechnological processes and, unlike CS, is not sulfated. It has been shown that CB to play a more significant role in the phenotypic maintenance of chondrocytes than chondroitin sulfate and increases their viability and proliferation. A recent A Single-Arm, Open-Label, Pilot Study was conducted to evaluate the safety and efficacy of a single-dose intra-articular injection of Hybrid Hyaluronic acid and Sodium Chondroitin in the Treatment of Symptomatic Hip Osteoarthritis. A single injection of HS-SC was well tolerated and safe in the treatment of symptomatic hip OA. The treatment demonstrated a rapid significant improvement in pain (VAS) and function (Lequesne's Index) up to 6 months of follow-up.
Introduction and Objective
A proper restoration of hip biomechanics is fundamental to achieve satisfactory outcomes after total hip arthroplasty (THA). A global hip offset (GO) postoperatively reduction of more than 5 mm was known to impair hip functionality after THA. This study aimed to verify the restoration of the GO radiographic parameter after primary THA by the use of a cementless femoral stem available in three different offset options without length changing.
Materials and Methods
From a consecutive series of 201 patients (201 hips) underwent primary cementless THA in our centre with a minimum 3-year follow up, 80 patients (80 hips) were available for complete radiographic evaluation for GO and limb length (LL) and clinical evaluation with Harris hip score (HHS). All patients received the same femoral stem with three different offset options (option A with – 5 mm offset, option B and option C with + 5 mm offset, constant for each sizes) without changing stem length.
Introduction and Objective
Interest for direct anterior approach (DAA) in hip hemiarthroplasty (HHA) has greatly increased in recent years, however which is the best surgical approach in hip replacement treating femoral neck fractures (FNFs) is already unclear. The aim of this study is to perform a radiographic and perioperative complications analysis by comparing the direct anterior approach (DAA) with the direct lateral approach (DLA) in patients treated with hemiarthroplasty for FNFs.
Materials and Methods
Patients with FNFs surgically treated between 2016–2020 with HHA were enrolled. The radiographical outcomes of DAA and DLA are compared. Several peri-operative and post-operative variables were evaluated: mean surgery time, complications as periprosthetic fractures or episodes of dislocation, the average of post-operative diaphyseal filling of the stem (Canal Fill Index, CFI), the extent of heterotopic ossification (HO) (simplified Broker classification) and metadiaphiseal bone loss (Paprosky classification) within one year from surgery.
Introduction and Objective
The patients with a total hip arthroplasty is growing in world manly in Europe and USA, and this solution present a high success at 10years in several orthopaedic registers. The application of total press-fit hip fixation presents the most used solution, but presents some failures associated to the acetabular component fixation, associated to the load transfer and bone loss at long term. The aim of this work is to investigate the influence of different acetabular bone loss in the strain distribution in iliac bone. To evaluate implant fixation, an experimental study was performed using acetabular press-fit component simulating different acetabular bone loss and measuring the strain distribution.
Materials and Methods
The experimental samples developed was based in an iliac bone model of Sawbones supplier and a acetabular component Titanium (Stryker) in a condition press-fit fixation and was implanted according surgical procedure with 45º inclination angle and 20º in the anteversion angle. Were developed five models with same initial bone, one with intact condition simulating the cartilage between bones and four with different bone loss around the acetabular component. These four models representing the evolution of bone support of acetabular components presented in the literature. The evolution of bone loss was imposed with a CAD CAM process in same iliac bone model. The models were instrumented with 5 rosettes in critical region at the cortical bone to measure the strain evolution along the process.
Introduction and Objective
The surgical strategy for acetabular component revision is determined by available host bone stock. Acetabular bone deficiencies vary from cavitary or segmental defects to complete discontinuity. For segmental acetabular defects with more than 50% of the graft supporting the cup it is recommended the application of reinforcement ring or ilioischial antiprotrusio devices. Acetabular reconstruction with the use of the antiprotrusion cage (APC) and allografts represents a reliable procedure to manage severe periprosthetic deficiencies with highly successful long-term outcomes in revision arthroplasty.
Objective
We present our experience, results, critical issues and technical innovations aimed at improving survival rates of antiprotrusio cages.
Minimally invasive surgery for the restoration of bone tissues lost due to diseases and trauma is preferred by the health care system as the related costs are continuously increasing. Recently, efforts have been paid to optimize injectable calcium phosphate (CaP) cements which have been recognized as excellent alloplastic material for osseous augmentation because of their unique combination of osteoconductivity, biocompatibility and mouldability. The sol-gel synthesis approach appears to be the most suitable route towards performing injectable calcium phosphates. Different strategies used to prepare bioactive and osteoinductive injectable CaP are reported. CaP gels complexed with phosphoserine-tethered poly(ε-lysine) dendrons (G3-K PS) designed to interact with the ceramic phase and able to induce osteogenic differentiation of human mesenchymal stem cells (hMSCs) is discussed. Recently, attention has been given to the modification of hydroxyapatite with Strontium (Sr) due to its dual mode of action, simultaneously increasing bone formation (stimulating osteoblast differentiation) while decreasing bone resorption (inhibiting osteoclast differentiation). The effect of systems based on strontium modified hydroxyapatite (Sr-HA) at different composition on proliferation and osteogenic differentiation of hMSC is described. One more approach is based on the use of antimicrobial injectable materials. It has been demonstrated that some imidazolium, pyridinium and quaternary ammonium ionic liquids (IL) have antimicrobial activity against some different clinically significant bacterial and fungal pathogens. Here, we report several systems based on IL at different alkyl-chain length incorporated in Hydroxyapatite (HA) through the sol-gel process to obtain an injectable material with simultaneous opposite responses toward osteoblasts and microbial proliferation.
Introduction and Objective
Calcium phosphates are among the most commonly used bone graft substitute materials. Compositions containing predominantly monetite (∼84.7%) with smaller additions of beta-tricalcium phosphate (β-TCP; ∼8.3%) and calcium pyrophosphate (Ca-PP; ∼6.8%) have previously been demonstrated to exhibit osteoinductive properties. Such a multi-component calcium phosphate bioceramic was fashioned in the form of hollowed-out, dome-shaped devices (15 mm diameter, 4 mm height), each reinforced with a 3D printed Ti6Al4V ELI frame. With the aim to induce bone formation beyond the skeletal envelope, these devices were investigated in vivo using a sheep (Ovis aries) occipital bone model.
Materials and Methods
The bioceramic composition was prepared from a mixture of β-TCP/dicalcium pyrophosphate and monocalcium phosphate monohydrate powders mixed with glycerol. The Ti6Al4V ELI frame was positioned into a dome-shaped mould and bioceramic paste was poured over the frame and allowed to set, in sterile water, prior to removal from the mould. In adult female sheep (n=7), the devices were positioned directly over the bone and stabilised using self-drilling screws. After 52 weeks, the devices were retrieved, resin embedded, and used for X-ray micro-computed tomography (micro-CT), histology, backscattered electron scanning electron microscopy (BSE-SEM), energy dispersive X-ray spectroscopy (EDX), micro-Raman spectroscopy, and Fourier transform infrared spectroscopy (FTIR).
Introduction and Objective
The continued effectiveness of antibiotic loaded bone cements is threatened by antibiotic resistance. The common antiseptic, chlorhexidine (CHX), is a potential alternative to antibiotics in bone cements, but conventional salts are highly soluble, causing burst release and rapid decline to subinhibitory local CHX concentrations. Here, chlorhexidine triphosphate (CHX-TP), a low solubility CHX salt, is investigated as an alternative antimicrobial in PMMA bone cements. The aim was to assess duration of antimicrobial release and antimicrobial efficacy, along with handling, setting and mechanical properties of CHX-TP loaded cements, compared with an existing cement formulation containing gentamicin.
Materials and Methods
Palacos R (Heraeus Medical, Newbury, UK) with 0, 1, 4, 7 and 12% CHX-TP (w/w) cements were prepared by combining solid CHX-TP with Palacos R components, and compared with Palacos R+G. All cements were prepared without vacuum and under ISO 5833:2002 conditions. Cements were tested under ISO 5833:2002 for compressive and bending properties, setting time, maximum temperature and doughing time. Antimicrobial release from the cements into deionised water was studied and antimicrobial efficacy of unaged and aged cements against Staphylococcus aureus (ATCC 29213) was assessed using a disc diffusion assay.
Introduction and Objective
The choice of appropriate characteristics is crucial to favor a firm bonding between orthopedic implants and the host bone and to permit bone regeneration. In particular, the morphology and composition of the biointerface plays a crucial role in orchestrating precise cellular responses. Here, to modulate the biointerface, we propose new biomimetic coatings, having multi-scale nano- to micro- morphological cues and a composition mimicking the mineral phase of bone.
Materials and Methods
Films on various substrates are obtained by Ionized Jet Deposition (IJD), by ablation of biogenic apatite and annealing at 400°C for 1 hour. Films are proposed for functionalization of metallic implants, but application to heat sensitive porous (3D printed) substrates is also shown, as it permits to further boost biomimicry (by addition of collagen/gelatin), thus reproducing the architecture of cancellous bone. In IJD, coatings thickness can be selected by tuning deposition duration. Here, a 450 nm thickness is selected based on preliminary results. Micro-rough titanium alloy (Ti6Al4V) disks (roughness 5 μm) are used as a substrate for the deposition and as a control. The coatings are characterized in terms of composition (GI-XRD, EDS, FT-IR microscopy), morphology (FEG-SEM, AFM, data processing by ImageJ), mechanical properties (micro-scratch test) and dissolution profile in medium (pH 7.4, FEG-SEM). Then, their behavior is characterized in vitro (human bone marrow-derived mesenchymal stromal cells - hMSCs), by studying cells early adhesion (focal adhesion by vinculin staining), viability (Alamar Blue), morphology (SEM) and differentiation (expression of RUNX2, ALPL, SPARC and COL1A1, BMP2, BGLAP, osteocalcin, alkaline phosphatase, collagen type I) at 3, 7 and 14 days.
Introduction and Objective
Guided Bone Regeneration (GBR) uses biodegradable collagen membranes of animal origin tissues (dermis and pericardium). Their barrier effect prevents soft tissues to interfere with the regeneration of alveolar bone. However, their xenogeneic origin involves heavy chemical treatments which impact their bioactivity. Wharton's Jelly (WJ) from the umbilical cord is a recoverable surgery waste. WJ is mostly made from collagen fibers, proteoglycans, hyaluronic acid, and growth factors. WJ with immunologically privileged status and bioactive properties lends credence to its use as an allograft. Nevertheless, low mechanical properties limit its use in bone regenerative strategies. Herein, our objective is to develop a crosslinked WJ-based membrane to improve its strength and thus its potential use as a GBR membrane.
Materials and Methods
The umbilical cords are collected after delivery and then stored at −20°C until use. The WJ membranes (1 × 5 × 12 mm) were obtained after the removal of blood vessels and amniotic tissue, washed, lyophilized, and stored at −20°C. WJ membranes were incubated in genipin solutions in decreasing concentrations (0.3 g / 100 mL − 0.03 g / 100 mL) for 24 hours at 37°C. The crosslinking degree was estimated by ninhydrin and confirmed by FTIR (Fourier-transform infrared spectroscopy) assays. The swelling rate was obtained after the rehydration of dry crosslinked WJ-membrane for 10 min in D-PBS. The mechanical properties were assessed in hydrated conditions on a tensile bench. The resistance to the degradation was evaluated by collagenase digestion (1 mg/mL for 60 hours) assay. The cytotoxicity of crosslinked WJ-membrane was evaluated in accordance with the standard ISO.10993-5 (i.e. Mitochondrial activity and Lactate Dehydrogenase release) against Mesenchymal Stem Cells (MSCs). Finally, the MSCs colonization and proliferation were followed after 21 days of culture on crosslinked WJ-membranes.
The World Health Organisation (WHO) has included low back pain in its list of twelve priority diseases. Notably, Degenerative disc disease (DDD) presents a large, unmet medical need which results in a disabling loss of mechanical function. Today, no efficient therapy is available. Chronic cases often receive surgery, which may lead to biomechanical problems and accelerated degeneration of adjacent segments. Our consortium partners have developed and studied mesenchymal stem cell-based, regenerative therapies trials. In previous phase 2 trial, patients exhibited rapid and progressive improvement of functional and pain indexes after 1 year with no significant side effects. To develop the world's first rigorously proven, effective treatment of DDD, EUROSPINE aims to assess, via a multicentre, randomized, controlled, phase 2b clinical trial including 112 patients with DDD, the efficacy of an allogenic intervertebral mesenchymal stem cell (MSC)-based therapy. This innovative therapy aims to rapidly and sustainably (at least 24 months) reduce pain and disability. In addition, the consortium aims to provide new knowledge on immune response & safety associated with allogeneic BM-MSC intradiscal injection. This simple procedure would be cost-effective, minimally invasive, and standardised. At the end of the RESPINE trial, we aim to propose a broadly available and clinically applicable treatment for DDD, marketed by European SMEs.
Introduction and Objective
Osteoarthritis (OA) is the most common inflammatory and degenerative joint disease. Mesenchymal Stromal Cells (MSCs), with their chondro-protective and immune-regulatory properties, have been considered as a new approach to treat OA. Considering the risk of cell leakage outside the articular space and the poor survival rate after intra-articular (IA) injection, we hypothesized that cell encapsulation in cytoprotective hydrogels could overcome these limitations and provide cells with a suitable 3D microenvironment supporting their biological activity. We previously generated micromolded alginate particles (diameter 150 μm) and demonstrated the long-term viability of microencapsulated MSCs isolated from human adipose tissue (hASCs). Encapsulated cells maintained their in vitro ability to sense and respond to a pro-inflammatory environment (IFN-γ/TNF-α or synovial fluids from OA patients) by secreting PGE2, IDO, HGF and TGF-β. In this study, we evaluated the anti-OA efficacy of these microencapsulated hASCs in a post-traumatic OA model in rabbits.
Materials and Methods
OA was surgically induced by anterior cruciate ligament transection (ACLT)-mediated destabilization of the right knee in rabbits (n=24). Eight weeks after surgery, destabilized joints were injected (IA, 26G needle) with 200 μL of either PBS, blank microparticles, non-encapsulated or microencapsulated cells (5×105 cells). Six weeks after injection, rabbits were euthanized and all destabilized (right) and sham-operated (left contralateral) joints were dissected and analyzed for OA severity. Tibial subchondral bone histomorphometric parameters were measured by quantitative micro-computed tomography (micro-CT). Histological sections of samples were analyzed after Safranin-O staining and quantitatively assessed according to a modified Osteoarthritis Research Society International (OARSI) scoring system. Immunohistochemical detection of NITEGE was performed to assess the extracellular matrix degradation.
Introduction and Objective
Aneurysmal bone cyst (ABC) of the spine is a locally aggressive benign lesion which can be treated by en bloc resection with wide margin to reduce the risk of local recurrence. To avoid morbidity associated with surgery, selective arterial embolization (SAE) can be considered the first-line treatment for ABCs of the spine. Other emerging treatments for ABCs include bisphosphonates, percutaneous doxycycline, sclerotherapy and Denosumab. In addition, we previously introduced the use of autologous bone marrow concentrate (BMC) injection therapy to stimulate bone healing and regeneration in ABC of the spine. One of the potential advantages of such a method is that surgical treatments are not necessary, thus allowing for both a minimally invasive approach and the treatment of poorly accessible lesions. In this prospective study we described the clinical and radiological outcomes of percutaneous injection of autologous BMC in a series of patients affected by ABCs of the spine and followed for at least one year.
Materials and Methods
Fourteen patients (6 male, 8 female) were treated between June 2014 to December 2019 with BMC injection for ABC of the spine. The mean age was 17.85 years. The mean follow up was 37.4 months (range 12– 60 months). The dimension of the cyst and the degree of ossification were measured by Computed Tomography (CT) scans before the treatment and during follow-up visits.
Introduction and Objective
The use of microfragmented adipose tissue (mFAT) for the treatment of musculoskeletal disorders, especially osteoarthritis, is gaining popularity following the positive results reported in recent case series and clinical trials. The purpose of this study is to characterize mFAT in terms of structure, cell content and secretome (i.e. protein and microvescicles released as paracrine mediators), and to compare it with unprocessed lipoaspirate tissue, in order to understand the possible mechanisms of action and the benefit derived from tissue processing.
Materials and Methods
Unprocessed lipoaspirate (LA) and mFAT were obtained from 7 donors. Each tissue sample was divided in four aliquots: A) fixed in formalin for histological evaluation; B) enzymatically digested to harvest cells with the exclusion of adipocytes; C) cultured for 24 hours in serum-free DMEM to harvest secretome; D) freshly frozen for proteomic evaluation. Hematoxylin and eosin staning, as well as immunohistochemistry for CD31, CD90, CD146 were performed on aliquot A. Cell count, viability, senescence and immunophenotype were assessed on aliquot B. Culture medium from aliquot C was collected and used for proteomic analysis and micro-RNA extraction and quantitation from extracellular vesicles. Aliquot D was lysed, protein were extracted and analyzed using a high-throughput proteomic approach.
Introduction and Objective
Osteoarthritis (OA) represents one of the leading cause of disability all over the world. Cell therapies, mainly based on mesenchymal stem cells (MSCs), have shown to modulate the pathogenesis of OA in basic, preclinical and clinical studies. Adipose tissue (AT) have emerged as a rich and promising source of MSCs called adipose derived stem cells (ASCs). Different systems are available for processing lipoaspirate to purify the samples from oily and haemorrhagic fractions, minimizing the risk of complications and maximizing the biological yield for subsequent grafting. However, few studies compared the efficacy of the different processing devices already used in clinical practice. This study aims to characterize the products obtained by the use of two different systems such as micro-fragmentation or nano-fragmentation comparing them with the starting material (AT) and the collagenase isolated ASCs.
Materials and Methods
AT from 12 donors arrived without selection to the laboratories: 4 lipoaspirated (LA), 4 micro-fragmented (mF) and 4 nano-fragmented (nF). The samples were divided into three aliquots for paraffin embedding, RNA extraction and digestion with collagenase for ASCs isolation. Paraffin embedded tissue sections were stained with hematoxylin-eosin to analyze morphology. RNA was extracted, retro-transcribed and analyzed with real-time PCR to analyze the expression of pluripotency genes (SOX2, NANOG and POU5F1) and inflammatory genes (IL-1beta and iNOS). Data were analyzed using Graphpad Prism 8.0 and expressed as mean ± SD. One-way ANOVA followed by Tukey test was used to compare the different groups.
Some activities of daily living require that the head be kept level during axial rotation of the cervical spine (Kinematically Constrained Axial Rotation). One such activity is looking over one's shoulder when walking or driving. The kinematic constraint of keeping the head level during axial rotation means that the segmental axis of rotation may not be aligned with the global axis of rotation of the cervical spine. Most of the literature on cervical spine axial rotation is based on experiments where the segmental axis of rotation is aligned with the global axis of rotation (Traditional Axial Rotation). There are only a few clinical and biomechanical studies that have examined kinematically constrained cervical axial rotation. We performed a series of biomechanical experiments in which we tested cervical spines in traditional and kinematically constrained axial rotation. The resulting primary and coupled motions of the segments showed that kinematically constrained axial rotation is distinct from traditional axial rotation. Our findings and the findings of other kinematically constrained axial rotation studies will be compared and contrasted with data from traditional axial rotation studies.
Introduction and Objective
Trochanteric fractures are associated with increasing incidence and represent serious adverse effect of osteoporosis. Their cephalomedullary nailing in poor bone stock can be challenging and associated with insufficient implant fixation in the femoral head. Despite ongoing implant improvements, the rate of mechanical complications in the treatment of unstable trochanteric fractures is high. Recently, two novel concepts for nailing with use of a helical blade – with or without bone cement augmentation – or an interlocking screw have demonstrated advantages as compared with single screw systems regarding rotational stability and cut-out resistance. However, these two concepts have not been subjected to direct biomechanical comparison so far. The aims of this study were to investigate in a human cadaveric model with low bone density (1) the biomechanical competence of cephalomedullary nailing with use of a helical blade versus an interlocking screw, and (2) the effect of cement augmentation on the fixation strength of the helical blade.
Materials and Methods
Twelve osteoporotic and osteopenic femoral pairs were assigned for pairwise implantation using either short TFN-ADVANCED Proximal Femoral Nailing System (TFNA) with a helical blade head element, offering the option for cement augmentation, or short TRIGEN INTERTAN Intertrochanteric Antegrade Nail (InterTAN) with an interlocking screw. Six osteoporotic femora, implanted with TFNA, were augmented with 3 ml cement. Four study groups were created – group 1 (TFNA) paired with group 2 (InterTAN), and group 3 (TFNA augmented) paired with group 4 (InterTAN). An unstable pertrochanteric OTA/AO 31-A2.2 fracture was simulated. All specimens were biomechanically tested until failure under progressively increasing cyclic loading featuring physiologic loading trajectory, with monitoring via motion tracking.
Introduction and Objective
Intramedullary nails are frequently used for treatment of unstable distal tibia fractures. However, insufficient fixation of the distal fragment could result in delayed healing, malunion or nonunion. The quality of fixation may be adversely affected by the design of both the nail and locking screws, as well as by the fracture pattern and bone density. Recently, a novel concept for angular stable nailing has been developed that maintains the principle of relative stability and introduces improvements expected to reduce nail toggling, screw migration and secondary loss of reduction. It incorporates polyether ether ketone (PEEK) inlays integrated in the distal and proximal canal portions of the nail for angular stable screw locking. The nail can be used with new standard locking screws and low-profile retaining locking screws, both designed to enhance cortical fixation. The low-profile screws are with threaded head, anchoring in the bone and increasing the surface contact area due to the head's increased diameter.
The objective of this study was to investigate the biomechanical competence of the novel angular stable intramedullary nail concept for treatment of unstable distal tibia fractures, compared with four other nail designs in an artificial bone model under dynamic loading.
Materials and Methods
The distal 70 mm of thirty artificial tibiae (Synbone) were assigned to 5 groups for distal locking using either four different commercially available nails – group 1: Expert Tibia Nail (DePuy Synthes); group 2: TRIGEN META-NAIL with Internal Hex Captured Screws (Smith & Nephew); group 3: T2 Alpha with Locking Screws (Stryker); group 4: Natural Nail System featuring StabiliZe Technology (Zimmer) – or the novel angular stable TN-Advanced nail with low-profile screws (group 5, DePuy Synthes). The distal locking in all groups was performed using 2 mediolateral screws. All specimens were biomechanically tested under quasi-static and progressively increasing combined cyclic axial and torsional loading in internal rotation until failure, with monitoring by means of motion tracking.
Introduction and Objective
Gait variability is the amplitude of the fluctuations in the time series with respect to the mean of kinematic (e.g., joint angles) or kinetic (e.g., joint moments) measurements. Although gait variability increases with normal ageing or pathological mechanisms, such as knee osteoarthritis (OA). The purpose was to determine if a patient who underwent a total knee arthroplasty (TKA) can reduce gait variability.
Materials and Methods
Twenty-five patients awaiting TKA were randomly assigned to receive either medial pivot (MP, m=7/f=6, age=62.4±6.2 years) or posterior stabilized (PS, m=7/f=5, age=63.7±8.9 years) implants, and were compared to 13 controls (CTRL, m=7/f=6, age=63.9±4.3 years). All patients completed a gait analysis within one month prior and 12 months following surgery, CTRLs completed the protocol once. A waveform F-Test Method (WFM) was used to compare the variance in knee biomechanics variables at each interval of the gait cycle.
Introduction and Objective
Zone 2 flexor tendon injuries are still one of the challenges for hand surgeons. It is not always possible to achieve perfect results in hand functions after these injuries. There is no consensus in the literature regarding the treatment of zone 2 flexor tendon injuries, tendon repair and surgical technique to be applied to the A2 pulley. The narrow fibro-osseous canal structure in zone 2 can cause adhesions and loss of motion due to the increase in tendon volume due to surgical repair. Different surgical techniques have been defined to prevent this situation. In our study, in the treatment of zone 2 flexor tendon injuries; Among the surgical techniques to be performed in addition to FDP tendon repair; We aimed to compare the biomechanical results of single FDS slip repair, A2 pulley release and two different pulley plasty methods (Kapandji and V-Y pulley plasty).
Materials and Methods
In our study, 12 human upper extremity cadavers preserved with modified Larssen solution (MLS) and amputated at the mid ½ level of the arm were used. A total of 36 fingers (second, third and the fourth fingers were used for each cadaver) were divided into four groups and 9 fingers were used for each group. With the finger fully flexed, the FDS and FDP tendons were cut right in the middle of the A2 pulley and repaired with the cruciate four-strand technique. The surgical techniques described above were applied to the groups. Photographs of fingers with different loads (50 – 700 gr) were taken before and after the application. Proximal interphalangeal (PIP) joint angle, PIP joint maximum flexion angle and bowstring distance were measured. The gliding coefficient was calculated by applying the PIP joint angle to the single-phase exponential association equation.
In the past decades, a huge amount of effort has been devoted to translate evidence based on standard preclinical models of bone tumours to effective tools for clinical applications. Although cancer is a genetic disease, hence the emphasis on -omics approaches, the complexity of cancer tissue, a mix of competing clones of transformed elements that react differently to microenvironmental stimuli, may hardly be reproduced by standard approaches. Cost, biological differences and ethical concerns are increasingly recognized as weaknessess of animal models. To overcome these limitations and provide reliable, reproducible, and affordable tools for predicting the effectiveness of treatments, environmental-controlled 3D cultures and co-cultures (spheroids, organoids) coupled with microfluidics and advanced imaging have recently being considered as effective instrument to increase knowledge on the pathophysiology of bone tumours and define effective therapeutic solutions.
Introduction and Objective
Bone remodelling is a continuous process whereby osteocytes regulate the activity of osteoblasts and osteoclasts to repair loading-induced microdamage. While many in vitro studies have established the role of paracrine factors (e.g., RANKL/OPG) and cellular pathways involved in bone homeostasis, these techniques are generally limited to two-dimensional cell culture, which neglects the role of the native extracellular matrix in maintaining the phenotype of osteocyte. Recently, ex vivo models have been used to understand cell physiology and mechanobiology in the presence of the native matrix. Such approaches could be applicable to study the mechanisms of bone repair, whilst also enabling exploration of biomechanical cues. However, to date an ex vivo model of bone remodelling in cortical bone has not been developed. In this study, the objective was to develop an ex vivo model where cortical bone was subjected to cyclic strains to study the remodelling of bone.
Materials and Methods
Ex vivo model of bone remodelling induced by cyclic loading: At the day of culling, beam-shape bovine bone samples were cut and preserved in PBS + 5% Pen/Strep + 2 mM L-Glut overnight at 37°C. Cyclic strains were applied with a three-point bend system to induce damage with a regime at 16.66 mm/min for 5,000 cycles in sterile PBS in Evolve® bags (maximum strain 6%). A control group was cultured under static conditions.
Metabolic activity: Alamar Blue assays were performed after 1 and 7 days of ex vivo culture for each group (Static, Loaded) and normalized to weight.
Bone remodelling: ALP activity was assessed in the media at day 1 and 7. After 24 hours cell culture conditioned media (CM) was collected from each group and stored at −80°C. RAW264.7 cells were cultured with CM for 6 days, after which the samples were stained for TRAP, to determine osteoclastogenesis, and imaged.
Histomorphometry: Samples were cultured with calcein for 3 days to label bone formation between day 4 and 7. Fluorescent images were captured at day 7. μCT scanning was performed at 3 μm resolution after labelling samples with BaSO4 precipitate to quantify bone damage.
Introduction and Objective
Senescent bone cell overburden accelerates osteoporosis. Epigenetic alteration, including microRNA signalling and DND methylation, is one of prominent features of cellular senescence. This study aimed to investigate what role microRNA-29a signalling may play in the development of senile osteoporosis.
Materials and Methods
Bone biopsy and serum were harvested from 13 young patients and 15 senior patients who required spine surgery. Bone mass, microstructure, and biomechanics of miR-29a knockout mice (miR-29aKO) and miR-29a transgenic mice (miR-29aTg) were probed using mCT imaging and three-point bending material test. Senescent cells were probed using senescence-associated b-galactosidase (SA-b-gal) staining. Transcriptomic landscapes of osteoblasts were characterized using whole genome microarray and KEGG bioinformatics. miR-29a and senescence markers p16INK4a, p21Waf/cipl and inflammatory cytokines were quantified using RT-PCR. DNA methylome was probed using methylation-specific PCR and 5-methylcytosine immunoblotting.
Introduction and Objective
Klinefelter Syndrome (KS, karyotype 47,XXY) is the most frequent chromosomal aneuploidy in males, as well as the most common cause of infertility in men. Patients suffer from a lack of testosterone, i.e. hypergonadotropic hypogonadism provoking infertility, but KS men also show an increased predisposition to osteoporosis and a higher risk of bone fracture. In a mouse model for human KS, bone analysis of adult mice revealed a decrease in bone mass that could not be rescued by testosterone replacement, suggesting a gene dosage effect originating from the supernumerary X-chromosome on bone metabolism. Usually, X chromosome inactivation (XCI) compensates for the dosage imbalance of X-chromosomal genes between sexes. Some studies suggested that expression of genes that escape silencing of the supernumerary X-chromosome (e.g. androgen receptor) has an impact on sex differences, but may also cause pathological changes in males. As a promising new such candidate for a musculoskeletal escape gene, we identified the integral membrane protein (ITM) 2a, which is encoded on the X-chromosome and related to enchondral ossification. The aim of the project was to characterize systemic bone loss in the course of aging in our KS mouse model, and whether the supernumerary X-chromosome causes differences in expression of genes related to bone development.
Materials and Methods
Bone structure of 24 month (=aged) old male wild type (WT) and 41, XXY mice (B6Ei.Lt-Y) were analysed by μCT. Afterwards bones were paraffin embedded and cut. In addition, tissue of brain, liver, kidney, lung and heart were also isolated and embedded for IHC staining. Using an anti-ITM2a antibody, expression and cellular localization of ITM2a was evaluated. IHC was also performed on musculoskeletal tissue of WT embryos (E18.5) and neonatal mice to determine possible age-related differences.
Introduction and Objective
Some periprosthetic femoral fractures (PFFs) present history and radiographic aspect consistent with an atypical femoral fracture (AFF), fulfilling the criteria for AFF except that PFFs by themselves are excluded from the diagnosis of AFFs. The aim of this study was to evaluate in a single Institution series of PFFs if any of them could be considered a periprosthetic atypical femoral fracture (PAFF), and their prevalence.
Materials and Methods
Surgical records were searched for PFFs around a primary hip stem from January 2013 to December 2019. Cases were classified according to Vancouver classification. Demographic and medical history were extracted. Fisher's exact test was used for statistical analysis.
Orthopedic device-related bone infection is one of the most distressing complications of the surgical fixation of fractures. Despite best practice in medical and surgical interventions, the rate of infection remains stubbornly persistent, and current estimates indicate that treatment failure rates are also significant. As we approach the limit of the effectiveness of current anti-infective preventative and therapeutic strategies, novel approaches to infection management assume great importance. This presentation will describe our efforts to develop and test various hydrogels to serve as customized antibiotic delivery vehicles for infection prevention and treatment. Hydrogels offer solutions for many of the challenges faced by complex trauma wounds as they are not restricted spatially within a poorly defined surgical field, they often degrade rapidly with no compatibility issues, and releases 100% of the loaded antibiotic. The preliminary data set proving efficacy in preventing and treating infection in both rabbit and sheep studies will be described, including local antibiotic concentrations in the intramedullary canal over time, compared to that of the more conventional antibiotic loaded bone cement. These two technologies show potential for the prevention and treatment of infection in trauma patients, with a clear focus on optimized antibiotic delivery tailored for complex wounds.
Introduction and Objective
Digital infra-red thermography may have the capability of identifying local inflammations. Nevertheless, the role of thermography in diagnosing pin site infection has not been explored yet and the reliability and validity of this method for pin site surveillance is in question. The purpose of this study was to explore the capability and intra-rater reliability of thermography in detecting pin site infection.
Materials and Methods
This explorative proof of concept study follows GRRAS -guidelines for reporting reliability and agreement studies. After clinical assessment of pin sites by one examiner using Modified Gordon Pin Infection Classification (Grade 0 – 6), thermographic images of the pin sites were captured with a FLIR C3 camera and analyzed by the FLIR tools software package. The maximum skin temperature around the pin site and the maximum temperature for the whole thermographic picture was measured. Intra-rater agreement was established and test-retests were performed with different camera angles.
Introduction and Objective
Septic arthritis is an acute infective presentation of the joint calling for urgent intervention, thus making the differential diagnosis process difficult. An increase in temperature in the area containing the suspected septic arthritis is one of the clinically important findings. In this study, it was aimed to investigate whether or not the temperature changes obtained through thermal camera can be used as a new additional diagnostic tool in the differential diagnosis of septic arthritis.
Materials and Methods
The study was approved by the local ethics committee as a prospective cohort. A total of 49 patients, 15 septic and 34 non-septic ones, both male and female ones from all ages admitted to the emergency room or evaluated with the consultation of another clinics who were also present with a pre-diagnosis of arthritis (septic or non-septic) in the knee (with complaints of redness, swelling, pain, effusion, increased temperature, edema, and inability to walk) were included in the study. The patients with non-joint inflammatory problems and a history of surgery in the same joint were excluded from the study. The temperature increase in the joint area with suspected septic arthritis was observed, and the difference in temperature changes of this suspicious area with the joint area of the contralateral extremity was compared after which the diagnosis of septic arthritis was confirmed by taking culture with routine intra-articular fluid aspiration, which is the gold standard for definitive diagnosis.
Introduction and Objective
Management of bone loss associated with bone contamination or infection represents a double biological and clinical challenge frequent in traumatology. The advent of new biomaterials can allow a different approach in the treatment of bone gap. The purpose of this study was to evaluate the prophylactic and therapeutic effectiveness of addition of a new absorbable bone substitute (BS) eluting different antibiotics in reconstruction of bone defects after infections and fractures with soft tissue damage.
Materials and Methods
We conducted a review of patients with contaminated or infected bone defects treated using a new biomaterial, a porous composite of collagen matrices and Beta tricalcium phosphate (β TCP), able to provide a long-term release of different antibiotics. We have included treatment of osteomyelitis and osteosynthesis of exposed fracture (Gustilo Anderson 1–3b) or fractures with soft tissue damage and high risk of contamination. Surgical technique included debridement filling bone defect with BS eluting antibiotics, osteosynthesis (plate, nail, external fixator, kirschner wire), soft tissue coverage, and systemic antibiotic therapy. Radiographic and clinical data including complications (wound dehiscence, superficial or deep infection, osteomyelitis) were collected.
Introduction and Objective
Found in bone-associated prosthesis, Cutibacterium acnes (C. acnes) is isolated in more than 50% of osteoarticular prosthesis infections, particularly those involving shoulder prostheses. Ongoing controversies exist concerning the origin of C. acnes infection. Few reports construct a reasonable hypothesis about probable contaminant displaced from the superficial skin into the surgical wound. Indeed, despite strict aseptic procedures, transecting the sebaceous glands after incision might result in C. acnes leakage into the surgical wound. More recently, the presence of commensal C. acnes in deep intra-articular tissues was reported. C. acnes was thus detected in the intracellular compartment of macrophages and stromal cells in 62.5% of the tested patients who did not undergo skin penetration. Among bone stromal cells, mesenchymal stem cells (MSCs) are predominantly found in bone marrow and periosteum. MSCs are the source of osteogenic lines of cells capable of forming bone matter. In this study, the pathogenicity of C. acnes in bone repair context was investigated.
Materials and Methods
Human bone marrow derived MSCs were challenged with C. acnes clinical strains harvested from non-infected bone site (Cb). The behaviour of Cb strain was compared to C. acnes took from orthopaedic implant-associated infection (Ci). The infective capabilities of both strains was determined following gentamicin-based antibiotic protection assay. The morphology and ultrastructural analysis of infected MSCs was performed respectively through CLSM pictures of Phalloidin® stained MSCs cytoskeleton and DAPI labelled Cb, and transmission and scanning electron microscopies. The virulence of intracellular Ci and Cb (Ci-MSCs and Cb-MSCs) was investigated by biofilm formation on non-living bone materials; and the immunomodulatory response of infected MSCs was investigated (PGE-2 and IDO secretion detected by ELISA). Bone cells (osteoblasts and PMA differentiated macrophages) were then challenged with Cb-MSCs and Ci-MSCs. Intracellular accumulation of ROS within infected macrophages was assessed by flow cytometry after 2 h of infection and the catalase production by Cb-MSC and Ci-MSC was evaluated. Statistical analyses were performed using Mann & Whitney test.
The knee joint has also a periarticular adipose tissue, which is known as Hoffa's fat pad (IPFP). IPFP has a dual function in the joint it reduces the concentration of Nitric Oxide, the release of glycosaminoglycans and the expression of MMP1 in the cartilage, but it also contains MSC and macrophages. Our hypothesis is that synovial fluid contains elements, not all of which are understood, which act as messengers and alter the “homeostasis” of the knee and the metabolism of all the cellular components of the joint, including the MSC of Hoffa's fat pad, thus making them another piece in the puzzle as far as OA of the knee is concerned.
The IPFP of 37 patients with OA and 36 patients with ACL rupture were analyzed. Isolation, primary culture, and a functional and proteomic study of MSCs from IPFP were performed.
Our results show that OA of the knee, in its more severe phases, also affects the MSC's of IPFP, which is a new actor in the OA degenerative process and which can contribute to the origin, onset and progression of the disease. A differential protein profile between OA and ACL patients were identified.
Infrapatellar pad should be regarded as an adipose tissue with its own characteristics and it´s also able to produce and excrete important inflammatory mediators directly into the knee joint.
Introduction and Objective
Kinesiophobia, the fear of physical movement and activity related to injury vulnerability, has been linked to sub-optimal outcomes following total knee replacement (TKR). This systematic review has two aims: to define the relationship between kinesiophobia and functional outcomes, pain and range of motion following TKR, and to evaluate published treatments for kinesiophobia following TKR.
Materials and Methods
A primary search was performed in March 2020. English-language studies recruiting adult primary TKR patients, using the Tampa Scale of Kinesiophobia (TSK) were included. Study quality was assessed using the Newcastle Ottawa Scale for cohort or case control studies, and the Cochrane Collaboration Risk of Bias tool for randomised controlled trials.
Introduction and Objective
Difficult primary total knee arthroplasty (TKA) and revision TKA are high demanding procedures. Joint exposure is the first issue to face off, in order to achieve a good result. Aim of this study is to evaluate the clinical and radiological outcomes of a series of patients, who underwent TKA and revision TKA, where tibial tubercle osteotomy (TTO) was performed.
Materials and Methods
We retrospectively reviewed a cohort of 79 consecutives TKAs where TTO was performed, from our Institution registry. Patients were assessed clinically and radiographically at their last follow-up (mean, 7.4 ± 3.7 years). Clinical evaluation included the Knee Society Score (KSS), the pain visual analogue scale (VAS), and range of motion. Radiological assessment included the evaluation of radiolucent lines, osteolysis, cortical bone hypertrophy, time of bone healing of the TTO fragment, and the hardware complication.
Introduction and Objective
Evidence in literature is contradicting regarding outcomes of total knee arthroplasty (TKA) in post-traumatic osteoarthritis (PTOA) and whether they are inferior to TKA in primary osteoarthritis (OA). The aim of this review was to find out if any difference exists in the results of TKA between the two indications.
Materials and Methods
The electronic databases MEDLINE, EMBASE, The Cochrane Collaboration, and PubMed were searched and screened in duplicate for relevant studies. The selected studies were further subjected to quality assessment using the modified Coleman method. The primary outcome measure was patient reported outcome, and secondary outcome measures were infection, revision, stiffness, and patella tendon rupture.
Introduction and Objective
TKA have shown both excellent long-term survival rate and symptoms and knee function improvement. Despite the good results, the literature reports dissatisfaction rates around 20%.
This rate of dissatisfaction could be due to the overstuff that mechanically aligned prostheses could produce during the range of motion. Either size discrepancy between bone resection and prosthetic component and constitutional mechanical tibiofemoral alignment (MTFA) alteration might increase soft tissue tension within the joint, inducing pain and functional limitation.
Materials and Methods
Total knee arthroplasties performed between July 2019 and September 2020 were examined and then divided into two groups based on the presence (Group A) or absence (Group B) of patellofemoral overstuff, defined as a thickness difference of more than 2 mm between chosen component and bone resection performed, taking into account at least one of the following: femoral medial and lateral condyle, medial or lateral trochlea and patella. Based on pre and post-operative MTFA measurements, Group A was further divided into two subgroups whether the considered alignment was modified or not. Patients were assessed pre-operatively and at 6 months post-op using the Knee Society Score (KSS), Oxford Knee Score (OKS), Forgotten Joint Score (FJS), Visual Analogue Scale (VAS) and Range of Motion (ROM).
Treatment of large bone defects represents a great challenge for orthopedic surgeons. The main causes are congenital abnormalities, traumas, osteomyelitis and bone resection due to cancer. Each surgical method for bone reconstruction leads its own burden of complications. The gold standard is considered the autologous bone graft, either of cancellous or cortical origin, but due to graft resorption and a limitation for large defect, allograft techniques have been identified. In the bone defect, these include the placement of cadaver bone or cement spacer to create the ‘Biological Chamber’ to restore bone regeneration, according to the Masquelet technique.
We report eight patients, with large bone defect (for various etiologies and with an average size defect of 13.3 cm) in the lower and upper limbs, who underwent surgery at our Traumatology Department, between January 2019 and October 2020. Three patients were treated with both cortical and cancellous autologous bone grafts, while five received cortical or cement spacer allografts from donors. They underwent pre and postoperative radiographs and complete osseointegration was observed in all patients already undergoing monthly radiographic checks, with a restoration of length and range of motion.
In our study, both the two stage-Masquelet and the cortical bone graft from a cadaver donor proved to be valid techniques in patients with very extensive defects to reconstruct the defect, restore the length, minimize implant left in situ and achieve complete functional recovery.
Introduction and Objective
Joint malleolar fractures have been estimated around 9% of all fractures. They are characterized by different both early and late complications. Among the latter, arthrofibrosis and early secondary arthrosis represent the two most common ones. Moreover, these two complications could be considered related to each other. Their real cause is still under investigation, even if residual post-operative hematoma and acute post-traumatic synovitis appear to be the most accredited. Supporting this hypothesis, joint debridement and the evacuation of the post-operative hematoma could represent a possible solution. The aim of this prospective study is to evaluate the role of arthroscopic lavage and debridement during internal fixation in order to prevent late joint complications.
Materials and Methods
Sixty consecutive patients who reported dislocated articular ankle fractures with surgical indication of open reduction and internal fixation (ORIF) have been included in this study. 27 patients underwent ORIF surgery associated with arthroscopic washout and debridement, while 33 patients, representing the control group, underwent just internal reduction and osteosynthesis. Patients with pure dislocations, non-articular fractures, polytrauma, previous local trauma, metabolic and connective pathologies were excluded. Follow-up was performed at 40 days (T1), 3 (T2) and 6 months (T3) after trauma for all patients. If necessary, some have been re-evaluated 12 months after the trauma. Efficacy of the treatment was evaluated through the VAS scale, Maryland scale, search for local complications such as dehiscence or infections, and finally radiographic evaluation. T-Student was estimated in order to individuate statistical significance.
Introduction and Objective
Wide awake local anaesthetic no tourniquet (WALANT) is being used for a wide variety of hand and wrist surgery. It has recently been used in distal radius fracture fixation. The purpose of this systematic review and meta-analysis was to assess the effectiveness of the WALANT technique in open reduction internal fixation.
Materials and Methods
Pubmed, Embase, and Scopus databases were searched on 02/03/21 with the following search terms: radius, WALANT, local anesthetic, wide awake surgery. The primary outcome measure was conversion to general anaesthetic and mean intra-operative visual analogue scale (VAS) pain scores. Secondary measures were operative times, mean intraoperative blood loss, post-operative functional and radiological outcomes.
Introduction and Objective
Lower limb fractures are amongst the most common surgically managed orthopaedic injuries, with open reduction and internal fixation (ORIF) as the conventional method of treatment of the fibula. In recent years, dedicated intramedullary implants have emerged for fibula fixation in tandem with the move towards minimally invasive surgery in high-risk patients. This is the largest multicentre review to date with the aim of establishing the clinical outcomes following intramedullary nail (IMN) fixation of the fibula and to identify the absolute indication for fibula IMN fixation.
Materials and Methods
A retrospective study of adult patients in all UK hospitals, who underwent fibula nail fixation between 01/01/2018 and 31/10/2020 was performed. Primary outcome measures included time to union, infection rate, other post-operative complications associated with the fixation and length of hospital stay. The secondary outcome measure was to identify the indication for fibula nailing. Data tabulation was performed using Microsoft Excel and analysis was performed using SPSS Version 23 (SPSS Statistics).
Introduction and Objective
Slipped Capital Femoral Epiphysis (SCFE) is one of the most common hip disorders in children and is characterized by a proximal femoral deformity, resulting in early osteoarthritis. Several studies have suggested that SCFE patients after in situ fixation show an altered gait pattern. Early identification of gait alterations might lead to earlier intervention programs to prevent osteoarthritis. The aim of this study is to analyse gait alterations in SCFE patients after in situ fixation compared to typically developed children, using the Computer Assisted Rehabilitation Environment (CAREN) system.
Materials and Methods
This is a cross-sectional, multi-center case-control study in the Netherlands. Eight SCFE patients and eight age- and sex-matched typically developed were included from two hospitals. Primary outcomes were kinematic parameters (absolute joint angles), studied with gait analysis using statistical parametric mapping (SPM). Secondary outcomes were spatiotemporal parameters, the Notzli alpha angle, muscle activation patterns (EMG), and clinical questionnaires (VAS, Borg CR10, SF-36, and HOOS), analyzed using non-parametric statistical methods.
Design criteria for tissue-engineered materials in regenerative medicine include robust biological effectiveness, off-the-shelf availability, and scalable manufacturing under standardized conditions. For bone repair, existing strategies rely on primary autologous cells, associated with unpredictable performance, limited availability and complex logistic. Here, we report the manufacturing of engineered and devitalized human hypertrophic cartilage (HyC) as cell-free material inducing bone formation by recapitulating the developmental process of endochondral ossification. Our strategy relies on a customized human mesenchymal line expressing Bone Morphogenetic Protein-2 (BMP-2), critically required for robust chondrogenesis and concomitant extracellular matrix (ECM) enrichment. Following apoptosis-driven devitalization, lyophilization and storage, the resulting material exhibited unprecedented osteoinductive properties, unmatched by synthetic delivery of BMP-2 or by living engineered grafts. Scalability and pre-clinical efficacy were demonstrated by bioreactor-based production and subsequent orthotopic assessment. Our findings exemplify the broader paradigm of customized ECMs, engineered to activate specific regenerative processes by programming human cell lines as biological factory units.
Introduction and Objective
Several in vitro studies have shed light on the osteogenic and chondrogenic potential of graphene and its derivatives. Now it is possible to combine the different biomaterial properties of graphene and 3D printing scaffolds produced by tissue engineering for cartilage repair. Owing to the limited repair capacity of articular cartilage and bone, it is essential to develop tissue-engineered scaffolds for patients suffering from joint disease and trauma. However, chondral lesions cannot be considered independently of the underlying bone tissue. Both the microcirculation and the mechanical support provided with bone tissue must be repaired. One of the distinctive features that distinguish graphene from other nanomaterials is that it can have an inductive effect on both bone and cartilage tissue. In this study, the effect of different concentrations of graphene on the in vivo performance of single-layer poly-ε-caprolactone based-scaffolds is examined. Our hypothesis is that graphene nanoplatelet- containing, robocast PCL scaffolds can be an effective treatment option for large osteochondral defect treatment. For this purpose, different proportions of graphene- containing (1%,3%,5%,10 wt%) PCL scaffolds were studied in a 5mm diameter osteochondral defect model created in the rabbit knee.
Materials and Methods
In the study graphene-containing (1, 3, 5, 10 wt%), porous and oriented poly-ε-caprolactone-based scaffolds were prepared by robocasting method to use in the regeneration of large osteochondral defects. Methods: The scaffolds were implanted into the full-thickness osteochondral defect in a rabbit model to evaluate the regeneration of defect in vivo. For this purpose, twenty female New Zealand white rabbits were used and they were euthanized at 4 and 8 weeks of implantation. The reparative osteochondral tissues were harvested from rabbit distal femurs and then processed for gross appearance assessment, radiographic imaging, histopathological and immunohistochemical examinations.
Introduction and Objective
Bone is a tissue which continually regenerates and also having the ability to heal after injuries however, healing of large defects requires intensive surgical treatment. Bioactive glasses are unique materials that can be utilized in both bone and skin regeneration and repair. They are degradable in physiological fluids and have osteoconductive, osteoinductive and osteostimulative properties. Osteoinductive growth factors such as Bone Morphogenetic Proteins (BMP), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), Transforming Growth Factor (TGF) are well known to stimulate new bone formation and regeneration. Unfortunately, the synthesis of these factors is not cost- effective and, the broad application of growth factors is limited by their poor stability in the scaffolds. Instead, it is wise to incorporate osteoinductive nanomaterials such as graphene nanoplatelets into the structures of synthetic scaffolds. In this study, borate-based 13-93B3 bioactive glass scaffolds were prepared by polymer foam replication method and they were coated with graphene-containing poly (ε-caprolactone) layer to support the bone repair and regeneration.
Materials and Methods
Effects of graphene concentration (1, 3, 5, 10 wt%) on the healing of rat segmental femur defects were investigated in vivo using male Sprague–Dawley rats. Fabricated porous bioactive glass scaffolds were coated by graphene- containing polycaprolactone solution using dip coating method. The prepared 0, 1, 3, 5 and 10 wt% graphene nanoparticle-containing PCL-coated composite scaffolds were designated as BG, 1G-P-BG, 3G-P-BG, 5G-P-BG and 10G-P-BG, for each group (n: 4) respectively. Histopathological and immunohistochemical (bone morphogenetic protein, BMP-2; smooth muscle actin, SMA and alkaline phosphatase, ALP) examinations were made after 4 and 8 weeks of implantation.
Introduction and Objective
Mesenchymal stem cells (MSC) are attractive candidates for bone regeneration approaches. Benefits of MSC therapy are mainly attributed to paracrine effects via soluble factors, exerting both immunoregulatory and regenerative actions. Encapsulation of MSC in hydrogels prepared with extracellular matrix (ECM) proteins has been proposed as a strategy to enhance their survival and potentiate their function after implantation. Functional activity of MSC can be regulated by the physical and mechanical properties of their microenvironment. In this work, we investigated whether matrix stiffness can modulate the crosstalk between MSC encapsulated in collagen hydrogels with macrophages and osteoblasts.
Materials and Method
Collagen hydrogels with a final collagen concentration of 1.5, 3 and 6 mg/mL loaded with human MSC were prepared. Viscoelastic properties of hydrogels were measured in a controlled stress rheometer. Cell distribution into the hydrogels was examined using confocal microscopy and the levels of the immunomodulatory factors interleukin-6 (IL-6) and prostaglandin E2 (PGE2) released by MSC were quantified by immunoassays. To determine the effect of matrix stiffness on the immunomodulatory potential of MSC, human macrophages obtained from healthy blood were cultured in media conditioned by MSC in hydrogels. The involvement of IL-6 and PGE2 in MSC-mediated immunomodulation was investigated employing neutralizing antibodies. Finally, the influence of soluble factors released by MSC in hydrogels on bone-forming cells was studied using osteoblasts obtained from trabecular bone explants from patients with osteonecrosis of the femoral head during total hip arthroplasty.
Introduction
Articular cartilage injuries have a limited potential to heal and, over time, may lead to osteoarthritis, an inflammatory and degenerative joint disease associated with activity-related pain, swelling, and impaired mobility. Regeneration and restoration of the joint tissue functionality remain unmet challenges. Stem cell-based tissue engineering is a promising paradigm to treat cartilage degeneration. In this context, hydrogels have emerged as promising biomaterials, due to their biocompatibility, ability to mimic the tissue extracellular matrix and excellent permeability. Different stimulation strategies have been investigated to guarantee proper conditions for mesenchymal stem cell differentiation into chondrocytes, including growth factors, cell-cell interactions, and biomaterials. An interesting tool to facilitate chondrogenesis is external ultrasound stimulation. In particular, low-intensity pulsed ultrasound (LIPUS) has been demonstrated to have a role in regulating the differentiation of adipose mesenchymal stromal cells (ASCs). However, chondrogenic differentiation of ASCs has been never associated to a precisely measured ultrasound dose. In this study, we aimed to investigate whether dose-controlled LIPUS is able to influence chondrogenic differentiation of ASCs embedded in a 3D hydrogel.
Materials and Methods
Human adipose mesenchymal stromal cells at 2∗106 cells/mL were embedded in a hydrogel ratio 1:2 (VitroGel RGD®) and exposed to LIPUS stimulation (frequency: 1 MHz, intensity: 250 mW/cm2, duty cycle: 20%, pulse repetition frequency: 1 kHz, stimulation time: 5 min) in order to assess its influence on cell differentiation. Hydrogel-loaded ASCs were cultured and differentiated for 2, 7, 10 and 28 days. At each time point cell viability (Live&Dead), metabolic activity (Alamar Blue), cytotoxicity (LDH), gene expression (COL2, aggrecan, SOX9, and COL1), histology and immunohistochemistry (COL2, aggrecan, SOX9, and COL1) were evaluated respect to a non-stimulated control.
The function of the upper extremity is highly dependent on correlated motion of the shoulder. The shoulder can be affected by several diseases. The most common are: rotator cuff tear (RCT), shoulder instability, shoulder osteoarthritis and fractures. Rotator cuff disease is a common disorder. It has a high prevalence rate, causing high direct and indirect costs. The appropriate treatment for RCT is debated. The American Academy Orthopaedic Surgeons guidelines state that surgical repair is an option for patients with chronic, symptomatic full-thickness RCT, but the quality of evidence is unconvincing. Thus, the AAOS recommendations are inconclusive. We are performing a randomized controlled trial to compare surgical and conservative treatment of RCT, in term of functional outcomes, rotator cuff integrity, muscle atrophy and fatty degeneration. Shoulder instability occurs when the head of the upper arm bone is forced out of the shoulder socket. Shoulder instabilities have been classified according to the etiology, the direction of instability, or on combinations thereof. The Thomas and Matsen classification, which is currently the most commonly utilized classification, divides shoulder instability events into the traumatic, unidirectional, Bankart lesion, and surgery (TUBS) and the atraumatic, multidirectional, bilateral, rehabilitation, and capsular shift (AMBRI) categories. The acquired instability overstress surgery (AIOS) category was then added. Surgical procedures for shoulder instability includes arthroscopic capsuloplasty, remplissage, bone block procedure or Latarjet procedure. Reverse total shoulder arthroplasty (RTSA) represents a good solution for the management of patients with osteoarthritis or fracture of the proximal humerus, with associated severe osteoporosis and RC dysfunction.
Introduction and Objective
Curative resection of proximal humerus tumours is now possible in this era of limb salvage with endoprosthetic replacement considered as the preferred reconstructive option. However, it has also been linked with mechanical and non-mechanical failures such as stem fracture and aseptic loosening. One of the challenges is to ensure that implants will endure the mechanical strain under physiological loading conditions, especially crucial in long surviving patients. The objective is to investigate the effect of varying prosthesis length on the bone and implant stresses in a reconstructed humerus-prosthesis assembly after tumour resection using finite element (FE) modelling.
Methods
Computed tomography (CT) scans of 10 humeri were processed in Mimics 17 to create three-dimensional (3D) cortical and cancellous solid bone models. Endoprostheses of different lengths manufactured by Stryker were modelled using Solidworks 2020. The FE models were divided into four groups namely group A consisting of the intact humerus and groups B, C and D composed of humerus-prosthesis assemblies with a body length of 40, 100 and 120 mm respectively and were meshed using linear 4-noded tetrahedral elements in 3matic 13. The models were then imported into Abaqus CAE 6.14. Isotropic linear elastic behaviour with an elastic modulus of 13400, 2000 and 208 000 MPa were assigned to the cortical bone, cancellous bone and prosthesis respectively and a Poisson's ratio of 0.3 was assumed for each material. To represent the lifting of heavy objects and twisting motion, a tensile load of 200 N for axial loading and a 5 Nm torsional load for torsional loading was applied separately to the elbow joint surface with the glenohumeral joint fixed and with all contact interfaces defined as fully bonded. A comparative analysis against literature was performed to validate the intact model. Statistical analysis of the peak von Mises stress values collected from predicted stress contour plots was performed using a one-way repeated measure of analysis of variance (with a Bonferroni post hoc test) using SPSS Statistics 26. The average change in stress of the resected models from the intact state were then determined.
Introduction and Objective
The aim of this study was to evaluate whether CT-based pre-operative planning, integrated with intra-operative navigation could improve glenoid baseplate fixation and positioning by increasing screw length, reducing number of screws required to obtain fixation and increasing the use of augmented baseplate to gain the desired positioning. Reverse total shoulder arthroplasty (RSA) successfully restores shoulder function in different conditions. Glenoid baseplate fixation and positioning seem to be the most important factors influencing RSA survival. When scapular anatomy is distorted (primitive or secondary), optimal baseplate positioning and secure screw purchase can be challenging.
Materials and Methods
Twenty patients who underwent navigated RSA (oct 2018 and feb 2019) were compared retrospectively with twenty patients operated on with a conventional technique. All the procedures were performed by the same surgeon, using the same implant in cases of eccentric osteoarthritis or complete cuff tear. Exclusion criteria were: other diagnosis as proximal humeral fractures, post-traumatic OA previously treated operatively with hardware retention, revision shoulder arthroplasty.
Introduction and Objective
Total shoulder replacement is a common elective procedure offered to patients with end stage arthritis. While most patients experience significant pain relief and improved function within months of surgery, some remain unsatisfied because of residual pain or dissatisfaction with their functional status. Among these patients, when laboratory workup eliminates infection as a possibility, corticosteroid injection (CSI) into the joint space, or on the periprosthetic anatomic structures, is a common procedure used for symptom management. However, the efficacy and safety of this procedure has not been previously reported in shoulder literature.
Materials and Methods
A retrospective chart review identified primary TSA patients who subsequently received a CSI into a replaced shoulder from 2011 – 2018 by multiple surgeons. Patients receiving an injection underwent clinical exam, laboratory analysis to rule out infection, and radiographic evaluation prior to CSI. Demographic variables were recorded, and a patient satisfaction survey assessed the efficacy of the injection.
Introduction and Objective
Postoperative pain control in shoulder surgery is challenging even in arthroscopic procedures. Acute postoperative pain can last up to 48hrs despite using multimodal analgesia. Different techniques have been used to control acute pain following shoulder surgery. The most common technique currently used in shoulder surgery at the elective orthopaedic centre in Leeds is a combination of general anaesthetic (GA) and interscalene block (ISB). ISB maybe very effective, however, carries many risks and potential side effects such as brachial plexus injury and paralysis of the vagus and laryngeal recurrent nerves as well as cervical sympathetic nerve and pneumothorax. ISB can also be associated with higher incidence of neurological deficit compared to other peripheral nerve blocks; up to 14% at 10 days in some cases. As such we decided to examine the use of ISB for achieving pain control in our elective unit.
Materials and Methods
A prospective consecutive series of 217 patients undergoing shoulder surgery were studied. These were grouped into 10 groups. All procedures were arthroscopic apart from shoulder arthroplasty procedures such as hemiarthroplasty and total shoulder replacements (TSRs). The choice of regional anaesthesia was ISB with GA as standard practice. Visual analogue scores (VAS) at 0hrs, 1hr, 2hrs, 4hrs and 6hrs; and total opiates intake were recorded. A one-way single factor ANOVA was used as preferred statistical analytical method to determine whether there is a difference in VAS scores and total opiates intake amongst the groups. Postoperative analgesics were used for pain relief, although these were not standardised.
AO Spine Guideline for Using Osteobiologics in Spine Degeneration project is an international collaborative initiative to identify and evaluate evidence on existing use of osteobiologics in spine degenerative diseases. It aims to formulate clinically relevant and internationally applicable guidelines ensuring evidence-based, safe and effective use of osteobiologics. The current focus is the use of osteobiologics in anterior cervical discectomy and fusion surgeries.
The guideline development is planned in three phases. Phase 1- Evidence synthesis and Recommendation; Phase 2- Guideline with osteobiologics grading and Validation; Phase 3- Guideline dissemination and Development of a clinical decision support tool. The key questions formulating the guidelines for the use of osteobiologics will be addressed in a series of systematic reviews in Phase 1. The evidence synthesized by the systematic reviews will be assessed by Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology, including expert panel discussions to formulate a recommendation. In Phase 2, osteobiologics will be graded based on evidence and the grading will be integrated with the recommendation from Phase 1, and thus formulate a guideline. The guideline will be further validated by prospective clinical studies. In the third phase, dissemination of the proposed guideline and development of a decision support tool is planned.
AO-GO aims to bridge an important gap between quality of evidence and use of osteobiologics in spine fusion surgeries. With a holistic approach the guideline aims to facilitate evidence-based, patient-oriented decision-making process in clinical practice, thus stimulating further evidence-based studies regarding osteobiologics usage in spine surgeries.
Introduction and Objective
Pectus carinatum is a common congenital anterior chest wall deformity, characterized by outward protrusion of sternum and ribcage resulted from rib cartilage overgrowth. The protrusion may be symmetrical or asymmetrical. Pectus carinatum association with mitral valve diseases, Marfan's syndrome, and scoliosis enforces that poor connective tissue development as possible etiological factor. Despite the coexistence of pectus carinatum and scoliosis has attracted the attention of some researchers, the association between pectus carinatum and the other spinal deformities has not been studied comprehensively. The frequency of spinal deformity in patients with pectus carinatum and the mutual relationships of their subtypes are needed to be studied to determine the epidemiological character of the combined deformity and to plan patient evaluation and management. Our study aimed to investigate the association, define the incidence and evaluate the characteristics between different types of spinal deformities and Pectus carinatum.
Materials and Methods
Radiological and physical examinations were performed for 117 pectus carinatum patients in Marmara university hospital/Turkey in the years between 2006 and 2013. The incidence of spinal deformity was calculated. Spinal deformities were classified as scoliosis, kyphosis, kyphoscoliosis, and spinal asymmetry, whereas pectus carinatum were subdivided into symmetric and asymmetric subgroups. The relationship between spinal deformities and the symmetrical-asymmetric subtype of pectus excavatum was statistically analyzed, Pearson chi-square test was used to compare the association of qualitative data. The significance level was accepted as p <0.05. Lastly, the angular values of the deformities of scoliosis and kyphosis patients were measured using the Cobb method. In this way, the magnitude of the deformity was given as a numerical value.
Introduction and Objective
The treatment of severe deformities often requiring aggressive techniques such as vertebral resection and osteotomies with high comorbidity. To mitigate this risk, several methods have been used to achieve a partial reduction of stiff curves. The objective of this study was to evaluate and quantify the effectiveness of the Perioperative Halo-Gravity Traction (HGT) in the Treatment of Severe Spinal Deformity in Children.
Materials and Methods
A historical cohort of consecutive childs with severe spinal deformity who underwent to a perioperative HGT as a part of the treatment protocol. Minimum follow-up of 2 years. Demographic, clinical and radiological data, including time duration of perioperative HGT and Cobb angle in the coronal and sagittal plane. The radiological variables were measured before the placement of the halo, after placement of the halo, at the end of the period of traction, after surgery and in the final follow-up.
Introduction and Objective
Up to 30% of thoracolumbar (TL) fractures are missed in the emergency room. Failure to identify these fractures can result in neurological injuries up to 51% of the casesthis article aimed to clarify the incidence and risk factors of traumatic fractures in China. The China National Fracture Study (CNFS. Obtaining sagittal and anteroposterior radiographs of the TL spine are the first diagnostic step when suspecting a traumatic injury. In most cases, CT and/or MRI are needed to confirm the diagnosis. These are time and resource consuming. Thus, reliably detecting vertebral fractures in simple radiographic projections would have a significant impact. We aim to develop and validate a deep learning tool capable of detecting TL fractures on lateral radiographs of the spine. The clinical implementation of this tool is anticipated to reduce the rate of missed vertebral fractures in emergency rooms.
Materials and Methods
We collected sagittal radiographs, CT and MRI scans of the TL spine of 362 patients exhibiting traumatic vertebral fractures. Cases were excluded when CT and/or MRI where not available. The reference standard was set by an expert group of three spine surgeons who conjointly annotated (fracture/no-fracture and AO Classification) the sagittal radiographs of 171 cases. CT and/or MRI were used confirm the presence and type of the fracture in all cases. 302 cropped vertebral images were labelled “fracture” and 328 “no fracture”. After augmentation, this dataset was then used to train, validate, and test deep learning classifiers based on the ResNet18 and VGG16 architectures. To ensure that the model's prediction was based on the correct identification of the fracture zone, an Activation Map analysis was conducted.
Introduction and Objective
Posterior and transforaminal lumbar interbody fusion (PLIF, TLIF) represent the most popular techniques in performing an interbody fusion amongst spine surgeons. Pseudarthrosis, cage migration, subsidence or infection can occur, with subsequent failed surgery, persistent pain and patient’ bad quality of life. The goal of revision fusion surgery is to correct any previous technical errors avoiding surgical complications. The most safe and effective way is to choose a naive approach to the disc. Therefore, the anterior approach represents a suitable technique as a salvage operation. The aim of this study is to underline the technical advantages of the anterior retroperitoneal approach as a salvage procedure in failed PLIF/TLIF analyzing a series of 32 consecutive patients.
Materials and Methods
We performed a retrospective analysis of patients’ data in patients who underwent ALIF as a salvage procedure after failed PLIF/TLIF between April 2014 to December 2019. We recorded all peri-operative data. In all patients the index level was exposed with a minimally invasive anterior retroperitoneal approach.
Introduction and Objective
In recent studies, robotic-assisted surgical techniques for unicompartmental knee arthroplasty (UKA) have demonstrated superior implant positioning and limb alignment compared to a conventional technique. However, the impact of the robotic-assisted technique on clinical and functional outcomes is less clear. The aim of this study was to compare the gait parameters of UKA performed with conventional and image-free robotic-assisted techniques.
Materials and Methods
This prospective, single center study included 66 medial UKA, randomized to a robotic-assisted (n=33) or conventional technique (n=33). Gait analysis was performed on a treadmill at 6 months to identify changes in gait characteristics (walking speed, each degree-of-freedom: flexion–extension, abduction–adduction, internal-external rotation and anterior-posterior displacement). Clinical results were assessed at 6 months using the IKS score and the Forgotten Joint Score. Implants position was assessed on post-operative radiographs.
Introduction and Objective
Virtual Surgical Planning (VSP) is becoming an increasingly important means of improving skills acquisition, optimizing clinical outcomes, and promoting patient safety in orthopedics and traumatology. Pediatric Orthopedics (PO) often deals with the surgical treatment of congenital or acquired limbs and spine deformities during infancy. The objective is to restore function, improve aesthetics, and ensure proper residual growth of limbs and spine, using osteotomies, bone grafts, age-specific or custom-made hardware and implants.
Materials and Methods
Three-dimensional (3D) digital models were generated from Computed Tomography (CT) scans, using free open-source software, and the surgery was planned and simulated starting from the 3D digital model. 3D printed sterilizable models were fabricated using a low-cost 3D printer, and animations of the operation were generated with the aim to accurately explain the operation to parents. All procedures were successfully planned using our VSP method and the 3D printed models were used during the operation, improving the understanding of the severely abnormal bony anatomy.
Introduction and Objective
Total knee arthroplasty (TKA) is a frequently and increasingly performed surgery in the treatment of disabling knee osteoarthritis. The rising number of procedures and related revisions pose an increasing economic burden on health care systems. In an attempt to lower the revision rate due to component malalignment and soft tissue imbalance in TKA, robotic assistance (RA) has been introduced in the operating theatre. The primary objective of this study is to provide the results of a theoretical, preliminary cost-effectiveness analysis of RA TKA.
Materials and Methods
A Markov state-transition model was designed to model the health status of sixty-seven-year-old patients in need of TKA due to primary osteoarthritis over a twenty-year period following their knee joint replacement. Transitional probabilities and independent variables were extracted from existing literature. Patients’ state in the transition model was able to change on an annual basis. The main differences between the conventional and RA TKA were the outlier rate in the coronal plane and the cost of the procedure. In RA TKA, it was hypothesized that there were lower revision rates due to a lower outlier rate compared to conventional TKA.
Introduction and Objective
Over the past few years, a reorganization of the educational pathways has been promoted with the purpose of optimizing the acquisition of competences and their assessment, so as to reduce the risks to both health care professionals and end users. Virtual reality (VR) has been repeatedly tested, initially as a positive reinforcement for more traditional educational pathways and, more recently, as their potential substitute. The aim of this study was to demonstrate the potentiality of VR simulation training in spine surgery.
Materials and Methods
The VR simulator reproduced the lateral lumbar access to the spine. The simulation included a tutorial, the preoperative settings, and the surgical session with different levels of procedural complexity. A total of 10 users were recruited for this study: 3 senior surgeons (group A) and 7 orthopedic residents or junior orthopedic surgeons (group B). Each user completed the simulation twice.
Osteoarthritis (OA) is the most common type of arthritis and causes a significant deterioration in patients’ quality of life. The high prevalence of OA as well as the current lack of disease-modifying drugs led to a rise in regenerative medicine efforts. The hope is that this will provide a treatment modality with the ability to alter the course of OA via structural modifications of damaged articular cartilage (AC). Regenerative therapy in OA starts with the concept that administered cells may engraft to a lesion site and differentiate into chondrocytes. However, recent studies show that cells, particularly when injected in suspension, rapidly undergo apoptosis after exerting a transient paracrine effect. If the injected stem cells do not lead to structural improvements of a diseased joint, the high cost of cell therapy for OA cannot be justified, particularly when compared with other injection therapeutics such as corticosteroids and hyaluronic acid. Long-term survival of implanted cells that offer prolonged paracrine effects or possible engraftment is essential for a successful cell therapy that will offer durable structural improvements. In this talk, the history and current status of regenerative therapy in OA are summarized along with the conceptual strategy and future directionsfor a successful regenerative therapy that can provide structural modifications in OA.
Introduction and Objective
Management of gap non-union of the tibia, the major weight bearing bone of the leg remains controversial. The different internal fixation techniques are often weighed down by relatively high complication rates that include fractures which fail to heal (non-union). Minimally invasive techniques with ring fixators and bone transport (distraction osteogenesis) have come into picture as an alternative allowing alignment and stabilization, avoiding a graduated approach. This study was focused on fractures that result in a gap non-union of > 6 cm. Ilizarov technique was employed for management of such non-unions in this case series. The Ilizarov apparatus consists of rings, rods and kirschner wires that encloses the limb as a cylinder and uses kirschner wires to create tension allowing early weight bearing and stimulating bone growth. Ilizarov technique works on the principle of distraction osteogenesis, that is, pulling apart of bone to stimulate new bone growth. Usually, 4–5 rings are used in the setup depending on fracture site and pattern for stable fixation. In this study, we demonstrate effective bone transport and formation of gap non-union more than 6 cm in 10 patients using only 3 rings construct Ilizarov apparatus.
Materials and Methods
This case study was conducted at Dr. D. Y. Patil Medical Hospital, Navi Mumbai, Maharashtra, India. The study involved 10 patients with a non-union or gap > 6 cm after tibial fracture. 3 rings were used in the setup for the treatment of all the patients. Wires were passed percutaneously through the bone using a drill and the projecting ends of the wires were attached to the metal rings and tensioned to increase stability. The outcome of the study was measured using the Oxford Knee scoring system, Functional Mobility Scale, the American Foot and Ankle Score and Visual Analog Scale. Further, follow up of patients was done upto 2 years.
Introduction and Objective
Exosomal miRNA have been shown to regulate many myogenic and osteogenic pathways involved in injury repair and healing. It is also known that rehabilitation and exercise can improve muscle mass and bone growth. The mechanisms by which this occurs in vivo are well studied, but the impact exosomes and their associated miRNA cargo have is unclear. With this knowledge and question in mind, we hypothesized that C2C12 myoblasts subjected to in vitro mechanical stimulus (“exercise”) would exhibit improved exosome production and differentially expressed miRNA cargo when compared to their static (“unexercised”) counterparts.
Materials and Methods
C2C12 myoblasts were cultured using the FlexCell FX-5000TT bioreactor. Two exercise regimens were programmed: 1) low intensity regimen (LIR) (0–15% strain at 0.5 Hz for 24 hours) 2) high intensity interval regimen (HIIR) (12–22% strain at 1 Hz for 10 minutes followed by 50 minutes of rest repeated for 24 hours). Unexercised (static) cells were cultured in parallel. Exosomes were isolated using the Invitrogen Total Exosome Isolation Reagent. The Pierce BCA Protein Assay, System Bioscience's ExoELISA-ULTRA CD81 Kit and, SBI's ExoFlow-ONE EV labeling kit were used to confirm and quantify exosome number and protein concentration. The SBI Exo-NGS service was used to perform miRNA sequencing on isolated exosomes.
Introduction and Objective
Osteoarthritis of the knee joint is common in old age population in every part of world. Pain is the major source of disability in patients with osteoarthritis of the knee joint. Subchondral bone marrow is richly innervated with nociceptive pain fibers and may be a source of pain in patients with symptomatic degenerative joint disease. Current therapy for managing bone marrow oedema is core decompression (CD), combining core decompression and injection of hydroxyapatite cement or autologus chondrocyte supplementtion. But all of this work has been done in femoral head and authors documented good result with minimal complication. There are various studies in literature suggesting treatment to repair BME by restoring support and relieving abnormal stresses with accepted internal fixation and bone stimulating surgical techniques in relieving knee OA pain. In this study, we present efficacy of knee arthroscopy with adjunctive core decompression and supplementation with structural scaffold to improve self-rated visual analog scale (VAS) pain scores, rate of conversion to arthroplasty, and patient satisfaction levels.
Materials and Methods
The study included patients aged between 40 and 75 years old, with pain in the knee for at least six months, associated with high-signal MRI lesion on T2 sequences, on the tibia or femur. Trephine was used as the bone decompression instrument. Trephine has a diameter of 8–10 mm and operation with trephine requires that a cortical incision window be made prior to decompression treatment, thus necessitating strict disinfection. This procedure was done under spinal anesthesia. After diagnostic arthroscopy, decompression was done under C –ARM in desired area on MRI. After decompression, defect was filled with Poly ester urea's scaffold impregnated with BMAC.
Introduction and Objective
Platelet-Rich-plasma (PRP) has been used in combination with stem cells, from different sources, with encouraging results both in vitro and in vivo in osteochondral defects management. Adipose-derived Stem Cells (ADSCs) represents an ideal resource for their ease of isolation, abundance, proliferation and differentiation properties into different cell lineages. Furthermore, Stem Cells in the adipose tissue are more numerous than from other sources. Aim of this study was to evaluate the potential of ADSCs in enhancing the effect of arthroscopic mesenchymal stimulation combined with infiltration of PRP.
Materials and Methods
The study includes 82 patients. 41 patients were treated with knee arthroscopy, Steadman microfractures technique and intraoperative PRP infiltration, Group A. In the Group B, 41 patients were treated knee arthroscopy, Steadman microfractures and intraoperative infiltration of PRP and ADSCs (Group B). Group A was used as a control group. Inclusion criteria were: Age between 40 and 65 years, Outerbridge grade III-IV chondral lesions, Kellegren-Lawrence Grade I-II. Patient-reported outcome measures (PROMs) evaluated with KOOS, IKDC, VAS, SF-12 were assessed pre-operatively and at 3 weeks, 6 months, 1-year post-operative. 2 patients of Group A and 3 patients of Group B, with indication of Puddu plate removal after high tibial osteotomy (HTO), underwent an arthroscopic second look, after specific informed consent obtained. On this occasion, a bioptic sample was taken from the repair tissue of the chondral lesion previously treated with Steadman microfractures.
Geriatric syndromes could lead individuals to exhibit significant mobility and psychological deficits resulting in significant healthcare costs. Thus, identifying strategies to delay aging, or prevent progressive loss of tissue homeostasis could dramatically restore the function and independence of millions of elderly patients and significantly improve quality of life. One of the fundamental properties of aging is the accumulation of senescent cells and senescence associated secretory phenotypes (SASPs) that needs to be treated in wide range of therapeutics including orthobiologics. Senolytic compounds selectively target and kill senescent cells and inhibit anti-apoptotic pathways that are upregulated in senescent cells thereby inducing apoptotic cell death and abrogating systemic SASP factors. We have also shown that blocking fibrosis with Losartan (TGF-β1 blocker) can improve musculoskeletal healing and cartilage repair by reducing the amount of fibrosis. Thus, we hypothesize that administration of anti-fibrotic agents will enhance the beneficial effects of orthobiologics. The safety and efficacy of several senolytic and anti-fibrotic agents to delay age-related dysfunction and improve the function of orthobiologics have been demonstrated in a variety of animal models (in vivo). Overall, our innovative approaches target senescent cells (inflammation) and TGF-β1 (fibrosis) to enhance the clinical efficacy and use of orthobiologics for musculoskeletal repair. We will also discuss ongoing active clinical trials on orthobiologics to aiming at evaluating the safety and efficacy of senolytic agent (Fisetin) and anti-fibrotic agent (Losartan), used independently or in combination, to enhance the beneficial effects of orthobiologics for patients afflicted with musculoskeletal diseases and conditions.
Introduction and Objective
Achilles tendon defect is difficult problem for orthopedic surgeon, and therefore the development of new treatments is desirable. Platelet-rich fibrin (PRF), dense fibrin scaffold composed of a fibrin matrix containing many growth factors, is recently used as regenerative medicine preparation. However, few data are available on the usefulness of PRF on Achilles tendon healing after injury. The objective of this study is to examine whether PRF promotes the healing of Achilles tendon defect in vivo and evaluated the effects of PRF on tenocytes in vitro.
Materials and Methods
PRF were prepared from rats according to international guidelines on the literature. To create rat model for Achilles tendon defect, a 4-mm portion of the right Achilles tendon was completely resected, and PRF was placed into the gap in PRF group before sewing the gap with nylon sutures. To assess the histological healing of Achilles tendon defect, Bonar score was calculated using HE, Alcian-blue, and Picosirius-red staining section. Basso, Beattie, Bresnahan (BBB) score was used for the evaluation of motor functional recovery. Biomechanical properties including failure tensile load, ultimate tensile stress, breaking elongation, and elastic modulus were measured. We examined the effects of PRF on tenocytes isolated from rat Achilles tendon in vitro. The number of viable cells were measured by MTS assay, and immunostaining of ki-67 was used for detection of proliferative cells. Migration of tenocytes was evaluated by wound closure assay. Protein or gene expression level of extracellular matrix protein, such as collagen, were evaluated by immunoblotting, immunofluorescence, or PCR. Phosphorylation level of AKT, FGF receptor, or SMAD3 was determined by western blotting. Inhibitory experiments were performed using MK-2206 (AKT inhibitor), FIIN-2 (FGFR inhibitor), SB-431542 (TGF-B receptor inhibitor), or SIS3 (SMAD3 inhibitor). All p values presented are two-sided and p values < 0.05 were considered statistically significant.
Introduction and Objective
Chronic tendinopathy is a multifactorial disease and a common problem in both, athletes and the general population. Mechanical overload and in addition old age, adiposity, and metabolic disorders are among the risk factors for chronic tendinopathy but their role in the pathogenesis is not yet unequivocally clarified.
Materials and Methods
Achilles tendons of young (10 weeks) and old (100 weeks) female rats bred for high (HCR) and low (LCR) intrinsic aerobic exercise capacity were investigated. Both Achilles tendons of 28 rats were included and groups were young HCR, young LCR, old HCR, and old LCR (n = 7 tendons per group/method). In this rat model, genetically determined aerobic exercise capacity is associated with a certain phenotype as LCR show higher body weight and metabolic dysfunctions in comparison to HCR. Quantitative real-time PCR (qPCR) was used to evaluate alterations in gene expression. For histological analysis, semi-automated image analysis and histological scoring were performed.
Introduction and Objective
The rupture of the anterior cruciate ligament is a common sports injury and surgical reconstruction is often required to restore full function of the knee. Hamstring tendons are usually used as autografts. In addition to knee pain and stiffness, infections are feared complications after surgery. Incubation of the autograft in a vancomycin solution until implantation reduced the infection rate by about ten-fold. Recent studies showed no negative effect of vancomycin on the biomechanical properties of porcine tendons. A negative effect of high vancomycin concentrations on chondrocytes and osteoblast is reported, but the effect on tendon and tenocytes is not known.
Materials and Methods
Rat Achilles tendons or isolated tenocytes were incubated with an increasing concentration of vancomycin (0 – 10 mg). Tendons were incubated for 0 – 40 minutes, while tenoyctes were incubated for 20 minutes followed by culturing for up to 7 days. Cell viability was assessed with PrestoBlue Assay and live/dead stain. The potential effect of vancomycin on the expression of tendon specific genes and extracellular matrix (ECM) genes was quantified. Possible structural changes of the tendon are analyzed.
Introduction and Objective
In the elderly population, chronic rotator cuff tears are often associated with high re-rupture rates after surgical tendon refixation. Implant materials, especially in combination with additives are supposed to positively influence healing outcome. Furthermore, adequate mechanical properties are crucial. In order to realize degradable implants with high specific surface area, polycaprolactone (PCL) was chosen as basic material and processed by electrospinning to achieve a high surface area for growth factor implementation and subsequent cell attachment.
Materials and Methods
PCL (Mn approx. 80,000 g/mol) was used to generate fibre mats by electrospinning (relative collector velocity 8 m/s; flow rate of 4 ml/h). Mechanical analysis was performed according to EN ISO 527–2:2012 with test specimen 1BA (5 mm in diameter). Maximum force at failure (Fmax) as well as stiffness were evaluated. For preclinical in vivo testing, a coating with CS-g-PCL was performed to increase cellular adhesion and biological integration. Native and TGF-ß3 loaded mats were examined in a chronic rat tendon defect model with dissection of the M. infraspinatus, four week latency and following refixation at the humerus with different PCL-fibre mats (approval Nr. 33.12–42502–04–15/2015). After 8 weeks, rats were finalized and tendon-bone insertions were analyzed biomechanically and via histological methods.
Aim
This study aims to define the normal postoperative presepsin kinetics in patients undergoing primary cementless total hip replacement (THR).
Methods
Patients undergoing primary cementless THR at our Institute were recruited. At enrollment anthropometric data, smocking status, osteoarthritis stage according to Kellgren and
Lawrence, Harris Hip Score (HHS), drugs assumption and comorbidities were recorded. All the patients underwent serial blood tests, including complete blood count, presepsin (PS) and C-Reactive Protein (CRP) 24 hours before arthroplasty and at 24-, 48-, 72- and 96-hours postoperatively and at 3-, 6- and 12-months follow-up.
Statistical analysis was performed with SPSS v25.0 (SPSS Inc, Chicago, IL, USA). The Wilcoxon and Kruskal-Wallis tests followed by the Dunn multiple comparison post hoc tests were carried out. Correlations between PS, CRP and TOT were assessed using the Spearman rank correlation coefficient. P values below 0.05 were considered significant.
Introduction and Objective
Heterotopic ossification is the formation of extraskeletal mineralized tissue commonly associated with either trauma or surgery. While several mouse models have been developed to better characterize the pathologic progression of HO, no model currently exists to study HO of the hip, the most common location of acquired HO in patients. Owing to the unique biological mechanisms underpinning the formation of HO in different tissues, we sought to develop a model to study the post-surgical HO of the hip.
Materials and Methods
Wild-type mice C57BL/6J mice were used to study the procedure outcomes, while Pdgfra-CreERT2;mT/mG and Scx-GFP reporter animals were used for the lineage tracing experiments (total n=16 animals, male, 12 weeks old). An anterolateral approach to the hip was performed. Briefly, a 2 cm incision was made centered on the great trochanter and directed proximal to the iliac crest and distally over the lateral shaft of the femur. The joint was then reached following the intermuscular plane between the rectus femoris and gluteus medius muscles. After the joint was exposed, the articular cartilage was removed using a micropower drill with a 1.2 mm reamer. The medius gluteus and superficial fascia were then re-approximated with Vicryl 5-0 suture (Ethicon Inc, Somerville, NJ) and skin was then closed with Ethilon 5-0 suture (Ethicon Inc). Live high resolution XR imaging was performed every 2 wks to assess the skeletal tissues (Faxitron Bioptics, Tucson, AZ). The images were then scored using the Brooker classification. Ex-vivo microCT was conducted using a Skyscan 1275 scanner (Bruker-MicroCT, Kontich, Belgium). 3D reconstruction and analysis was performed using Dragonfly (ORS Inc., Montreal, Canada). For the histological analysis of specimens, Hematoxylin and Eosin (H&E), modified Goldner's Trichrome (GMT) stainings were performed. Reporter activity was assessed using fluorescent imaging.
Introduction and Objective
Ceramic on Ceramic bearings in Total Hip Arthroplasty (THA) afford a low friction coefficient, low wear rates and extreme hardness. Significant complications include hip squeak, ceramic fracture and poor polyethylene performance in revision procedures due to imbedding of abrasive microscopic ceramic fragments. We report on the results of this bearing at a minimum of 10 years.
Materials and Methods
A single-centre retrospective review of 449 THAs was performed. Primary outcome measures included aseptic revision and all-cause revision rates at a minimum of 10 years post operatively. Evaluation of functionality was performed with WOMAC and SF-36 scores which were performed pre-operatively and at intervals of 6 months, one year, 2 years, 5 years and 10 years post operatively.
Introduction and Objective
Despite pure alumina have shown excellent long-term results in patients undergoing total hip arthroplasty (THA), alumina matrix composites (AMCs) composed of alumina and zirconium oxide are more commonly used. There are no comparative studies between these two different ceramics. We performed a retrospective case-control study to compare results and associated complications between AMC from two manufacturers and those with pure alumina from another manufacturer.
Materials and Methods
480 uncemented THAs with ceramic on ceramic (CoC) bearing surfaces (288 men and 192 women; mean age of 54.1 ± 12.4 years), were implanted from 2010 to 2015. Group 1: 281 THAs with pure alumina; Group 2A: 142 with AMC bearing in a trabecular titanium cup. Group 2B: 57 hips with AMC bearing with a porous-coated cup.
Introduction and Objective
Several factors contribute to the duration of the hospital stay in patients that undergo to total hip arthroplasty (THA), either subjective or perioperative. However, no definite evidence has been provided on the role of any of these factors on the hospitalization length. The aim of this retrospective investigation is to evaluate the correlation between several preoperative and perioperative factors and the length of hospital stay (LOS) in patients that underwent elective total hip arthroplasty.
Materials and Methods
Medical records of patients that underwent THA since the beginning of 2016 to the end of 2018 were retrospectively screened. Demographics, comorbidities, renal function, whole blood count. and length of post-operative ward stay were retrieved. The association between clinical, biochemical and surgical factors and the length of hospital stay was explored by means of linear regression models.
Osteoarthritis (OA) is a painful and disabling chronic condition that constitutes a major challenge to health care worldwide. There is currently no cure for OA and the analgesic pharmaceuticals available do not offer adequate and sustained pain relief, often being associated with significant undesirable side effects. Another disease associated with degenerating joints is Intervertebral disc degeneration (IVDD) which is a leading cause of chronic back pain and loss of function. It is characterized by the loss of extracellular matrix, specifically proteoglycan and collagen, tissue dehydration, fissure development and loss of disc height, inflammation, endplate sclerosis, cell death and hyperinnervation of nociceptive nerve fibers. The adult human IVD seems incapable of intrinsic repair and there are currently no proven treatments to prevent, stop or even retard disc degeneration. Fusion is currently the most common surgical treatment of symptomatic disc disease. However, radiographic follow-up studies have revealed that many patients develop adjacent segment disc degeneration due to altered spine biomechanics. The development of safe and efficacious disease modifying OA drugs (DMOADs) that treat pain and inflammation in joints will improve our ability to control the disease. I addition, a biologic treatment of IVDD is desirable. This presentation will provide an overview of recent advances and future prospects of a multimodal biologic treatment of OA, and IVDD. We will focus on Link N, a naturally occurring peptide representing the N terminal region of link protein and the first 1–8 residues of Link N (short Link N, sLN) responsible for the biologic therapy in question.
Introduction and Objective
To estimate the prevalence of acetabular ossifications in the adult population with asymptomatic, morphologically normal hips at CT and to determine whether the presence of labral ossifications is associated with patient-related (sex, age, BMI), or hip-related parameters (joint space width, and cam- and pincer-type femoroacetabular impingement morphotype).
Materials and Methods
We prospectively included all patients undergoing thoracoabdominal CT over a 3-month period. After exclusion of patients with a clinical history of hip pathology and/or with signs of osteoarthritis on CT, we included a total of 150 hips from 75 patients. We analyzed the presence and the size of labral ossifications around the acetabular rim. The relationships between the size of labral ossifications and patient- and hip-related parameters were tested using multiple regression analysis.
Introduction and Objective
Knee osteoarthritis (KOA) is a frequent disease for which therapeutic possibilities are limited. In current recommendations, the first-line analgesic is acetaminophen. However, low efficacy of acetaminophen, frequently leads to the use of weak opioids (WO) despite their poor tolerance, especially in elderly patients. The primary objective was to compare the analgesic efficacy and safety of a new wearable transcutaneous electrical nerve stimulation (W-TENS) to weak opioids (WO) in the treatment of moderate to severe, nociceptive, chronic pain in knee osteoarthritis patients.
Materials and Methods
ArthroTENS study is a phase 3, non-inferiority, multicentric, prospective, randomized, single-blinded for primary efficacy outcome, controlled, in 2-parallel groups, clinical study comparing W-TENS versus WO over a 3-month controlled period with an additional, optional, non-controlled, 3-month follow-up for patients in W-TENS group. The co-primary outcome was KOA pain intensity (PI) at month 3 and the number of adverse events (AEs) over 3 months.
Introduction and Objective
Osteoarthristis (OA) has been associated with many genes and yet the genetic basis for this disease has never formally been established. Recent realization that epigenetic changes could be the underlying pathological mechanisms has helped to explain many complex multifactorial diseases with no clear genetic cause. We therefore asked whether epigenetics could also play a role in OA. We have previously shown that the DNA epigenetic modification, specifically the hydroxymethylation on cytosine (5hmC), undergoes a fivefold increase on OA-associated genes which are activated at OA onset. In this study, we further uncovered a set of 5hmC-mediated gene targets and their mechanistic link to OA progression.
Materials and Methods
We surgically induced OA on 4 to 6 months old Tet1−/− mice (Tet1tm1.1Jae, the Jackson laboratory) and wild-type littermates by performing destabilization of the medial meniscus (DMM) surgery. Joints were collected for histological assessment through blinded grading with the OARSI scoring system. Human articular chondrocytes were harvested from OA cartilage samples obtained during total knee arthroplasty or from grossly normal cartilage pieces obtained during notchplasty or debridement from patients undergoing anterior cruciate ligament (ACL) reconstruction with no history of OA symptoms, under approved Human subjects Institutional Review Board protocols. Bioinformatic analyses of RNA-sequencing and CCGG sequencing (reduced representation 5hmC profiling) were performed to identify TET1 target genes associated with OA progression. Several measurements were used to assess the effect of TET1 ablation on the phenotype of mouse cartilage tissue and human chondrocytes including, histological evaluation, and quantitative bone assessment by micro-CT imaging and multiplex cytokine analyses in the serum of mice in vivo (mouse 39-plex assay) and in the supernatant of human chondrocyte cultures (human 62-plex assay).
Introduction and Objective
Hyaluronic acid (HA) is an effective option for the treatment of osteoarthritis (OA) patients due to several properties such as normalization of the mechanical and rheological properties of the synovial fluid and amelioration of OA symptoms and joints function by promoting cartilage nutrition. Since OA progression is also significantly related to oxidative stress and reactive oxygen species (ROS), sodium succinate (SS) is envisioned as a promising compound for cartilage treatment by providing antioxidant defense able to normalize intracellular metabolism and tissue respiration via mitochondrial mechanism of action. The scope of this study was to investigate on an in vitro inflammatory model the efficacy of Diart® product, a combination of HA and SS.
Materials and Methods
Donor-matched chondrocytes and synoviocytes were obtained from KL 3–4 OA patients undergoing total knee replacement. At passage 4, inflammation was promoted with 1 ng/ml IL-1B for 48 hours in absence and presence of Diart® at 1:3 dilution rate. Nitric oxide (NO) from cell culture supernatant was measured by Griess reaction. Mitochondrial and cytoplasmatic ROS evaluation was assessed by flow cytometry with MitoSox and dichlorodihydrofluorescein diacetate (DCFDA) assays. Gene expression of inflammation/oxidative stress-related transcripts (MMP1/MMP3/INOS/COX2) was evaluated by qRT-PCR using TBP as reference.
Barriers to successful return to previous level of activity following Anterior Cruciate Ligament Recon-struction (ACLR) are multifactorial and recent research suggests that athletic performance deficits persist after completion of the rehabilitation course in a large percentage of patients. Thirty soccer athletes (26.9 ± 5.7 years old, male) with ACL injury were surgically treated with all-inside technique and semitendi-nosus tendon autograft. At 2 years from surgery, they were called back for clinical examination, self-reported psychological scores, and biomechanical outcomes (balance, strength, agility and velocity, and symmetry).
Nonparametric statistical tests have been adopted for group comparisons in terms of age, concomitant presence of meniscus tear, injury on dominant leg, presence of knee laxity, presence of varus/valgus, body sides, and return to different levels of sports. Athletes with lower psychological scores showed lesser values in terms of power, resistance and neuromuscular activity as compared to the ones with good psychological scores that showed, instead, better self-reported outcomes (TLKS, CRSQ) and low fear of reinjury (TSK). In the athletes who had a functional deficit in at least one subtest, a safe return to sports could not have been recommended. Our findings confirmed that demographics, physical function, and psychological factors were related to playing the preinjury level sport at mean 2 years after surgery, sup-porting the notion that returning to sport after surgery is multifactorial. A strict qualitative and quantitative assessment of athletes’ status should be performed at different follow-ups after surgery to guarantee a safe and controlled RTP.
Introduction and Objective
Hip fractures represent one of the most challenging injuries in orthopaedic practice due to the associated morbidity, mortality and the financial burden they impose on the health care systems. By many still considered as the gold standard in the management of intertrochanteric fractures, the Dynamic Hip Screw utilizes controlled collapse during weight bearing to stabilize the fracture. Despite being a highly successful device, mechanical failure rate is not uncommon. The most accepted intraoperative indicator for lag screw failure is the tip apex distance (TAD), yet lateral femoral wall thickness (LWT) is another evolving parameter for detecting the potential for lateral wall fracture with subsequent medialization and implant failure. The aim of this study is to determine the mean and cut off levels for LWT that warrant lateral wall fracture and the implications of that on implant failure, revision rates and implant choice.
Materials and Methods
This prospective cohort study included 42 patients with a mean age of 70.43y with intertrochanteric hip fractures treated with DHS fixation by the same consultant surgeon from April 2019 to December 2019. The study sample was calculated based on a confidence level of 90% and margin of error of 5%. Fracture types included in the study are 31A1 and 31A2 based on the AO/OTA classification system. LWT was assessed in all patients preoperatively using Surgimap (Nemaris, NY, USA) software. Patients were divided into two groups according to the post-operative integrity of the lateral femoral wall, where group (A) sustained a lateral femoral wall fracture intraoperatively or within 12 months after the index procedure, while in group (B) the lateral femoral wall remained intact. All patients were regularly followed up radiologically and clinically per the Harris Hip Score (HHS) for a period of 12 months.
Introduction and Objective
Geriatric patients with a fragility fracture of the hip (FFH) are especially prone to sarcopenia with poor functional outcomes and quality of life. We assessed the prevalence of sarcopenia in older South African patients with FFH. Risk factors for sarcopenia were also investigated
Materials and Methods
From August 1 to November 30, 2018, all older patients with FFH were invited to participate. Sarcopenia was diagnosed based on the revised criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Handgrip strength (HGS) and muscle strength were assessed. Muscle quantity was determined by dual-energy X-ray absorptiometry. Demographic information was collected, and 25-hydroxyvitamin D (25[OH]D) status was determined.
Introduction and Objective
When using radiation intraoperatively, a surgeon should aim to maintain the dose as low as reasonably achievable to obtain the diagnostic or therapeutic goal. The UK Health Protection Agency reported mean radiation dose-area-product (DAP) of 4 Gy cm2 for hip procedures. We aimed to investigate factors associated with increased radiation exposure in fixation of proximal femur fractures.
Materials and Methods
We assessed 369 neck of femur fractures between April 2019 and April 2020 in one district general hospital. Fractures were classified as extracapsular or intracapsular and into subtypes as per AO classification. Data was collected on type of fractures, implants used, level of surgeon, duration of surgery and DAP. Types of fractures were subclassified as complex (multifragmentary, subtrochanteric and reverse oblique) or simple.
Introduction and Objective
The most common paediatric orthopaedic injury requiring hospital admission is a femoral fracture. There is debate regarding the optimal surgical technique for fixing femoral diaphyseal fractures in children aged 4 to 12 years. The National Institute for Health and Care Excellence (NICE) and the American Academy of Orthopaedic Surgeons (AAOS) have issued relevant guidelines, however, there is limited evidence to support these. The aim of this study was to conduct a systematic review and meta-analysis to compare the complication rate following flexible intramedullary nailing (FIN), plate fixation and external fixation (EF) for traumatic femoral diaphyseal fractures in children aged 4 to 12.
Materials and Methods
We searched MEDLINE, EMBASE and CENTRAL databases for interventional and observational studies. Two independent reviewers screened, assessed quality and extracted data from the identified studies. The primary outcome was the risk of any complication. Secondary outcomes assessed the risk of pre-specified individual complications.
Introduction and Objective
The Cartilage Oligomeric Matrix Protein (COMP) is a glycoprotein that is elevated in patients with osteoarthritis. The elevation increases linearly with the radiological grade of osteoarthritis. The objective of this study was to study the levels of COMP in knee osteoarthritis in the Indian population and to correlate (establish ranges) with the specific radiological grade of osteoarthritis (Kellgreen and Lawrence grading). Since the radiological classification is subjective, the COMP levels would serve as a more objective way of classifying osteoarthritic joints.
Materials and Methods
We analysed the COMP levels by the Enzyme Linked Immunosorbent Assay (ELISA) method in 100 patients presenting to the outpatient clinic of our hospital, after obtaining due approvals. The radiographs of these patients were classified according to the Kellgreen-Lawrence grading by a senior orthopaedic surgeon.