The use of implant biomaterials for prosthetic reconstructive surgery and osteosynthesis is consolidated in the orthopaedic field, improving the quality of life of patients and allowing for healthy and better ageing. However, there is the lack of advanced innovative methods to investigate the potentialities of smart biomaterials, particularly for the study of local effects of implant and osteointegration. Despite the complex process of osseointegration is difficult to recreate in vitro, the growing challenges in developing alternative models require to set-up and validate new approaches. Aim of the present study is to evaluate an advanced in vitro tissue culture model of osteointegration of titanium implants in human trabecular bone. Cubic samples (1.5×1.5 cm) of trabecular bone were harvested as waste material from hip arthroplasty surgery (CE AVEC 829/2019/Sper/IOR); cylindrical defects (2 mm Ø, 6 mm length) were created, and tissue specimens assigned to the following groups: 1) empty defects- CTR-; 2) defects implanted with a cytotoxic copper pin (Merck cod. 326429)- CTR+; 3) defects implanted with standard titanium pins of 6 µm-rough (ZARE S.r.l) -Ti6. Tissue specimens were cultured in mini rotating bioreactors in standard conditions, weekly assessing viability. At the 8-week-timepoint, immunoenzymatic, microtomographic, histological and histomorphometric analyses were performed. The model was able to simulate the effects of implantation of the materials, showing a drop in viability in CTR+, differently from Ti6 which appears to have a trophic effect on the bone. MicroCT and histological analysis supported the results, with lower BV/TV and Tb.Th values observed in CTR- compared to CTR+ and Ti6 and signs of matrix and bone deposition at the implant site. The collected data suggest the reliability of the tested model which can recreate the osseointegration process in vitro and can therefore be used for preliminary evaluations to reduce and refine in vivo preclinical models. Acknowledgment: This work was supported by Emilia-Romagna Region for the project “Sviluppo di modelli biologici in vitro ed in silico per la valutazione e predizione dell'osteointegrazione di dispositivi medici da impianto nel tessuto osseo”

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. Results. We included 246 patients (=547 catheters). 115 (21%) femoral, 162 (30%) saphenous, 66 (12%) sciatic, and 204 (37%) popliteal sciatic nerve catheter were used. The median duration of a catheter was 3 days [IQR = 2 – 5]. The proportion of femoral, sciatic, saphenous, and popliteal nerve catheters with duration of more than two days was 81%, 79%, 73%, and 71% for, respectively. This proportion varied also between different subspecialties. 91% of the catheters remained in place for more than two days in amputations (n=56), 89% in pediatric surgery (n=79), 76% in trauma (n=217), 64% in foot and ankle surgery (n=129), and 59% in limb reconstructive surgery (n=66). The proportion of pain-free patients were 77 – 95% at rest, 63 – 88% at mobilization. 79 – 92% did not need increased opioid doses, and 50 – 67% did not require PRN opioid. 443 catheters (81%) were removed as planned. The cause of unplanned catheter removal was loss of efficacy in 69 (13%), dislodgement in 23 (4.2%), leakage in 8 (1.5%), and erythema in 4 catheters (0.73%). No major complication occurred. Conclusions. 81% of catheters remained in place until planned removal and opioid usage after surgery was lower than expected. Catheters were efficient in both adult and pediatric surgery; however, a variation was seen between orthopaedic subspecialities regarding duration of nerve catheter usage

After anterior cruciate ligament (ACL) rupture, reconstructive surgery with a hamstring tendon autograft is often performed. Despite overall good results, ACL re-rupture occurs in up to 10% of the patient population, increasing to 30% of the cases for patients aged under 20 years. This can be related to tissue remodelling in the first months to years after surgery, which compromises the graft's mechanical strength. Resident graft fibroblasts secrete matrix metalloproteinases (MMPs), which break down the collagen I extracellular matrix. After necrosis of these fibroblasts, myofibroblasts repopulate the graft, and deposit more collagen III rather than collagen I. Eventually, the cellular and matrix properties converge towards those of the native ACL, but full restoration of the ACL properties is not achieved. It is unknown how inter-patient differences in tissue remodelling capacity contribute to ACL graft rupture risk. This research measured patient-specific tissue remodelling-related properties of human hamstring tendon-derived cells in an in vitro micro-tissue platform, in order to identify potential biological predictors for graft rupture. Human hamstring tendon-derived cells were obtained from remnant autograft tissue after ACL reconstructions. These cells were seeded in collagen I gels on a micro-tissue platform to assess inter-patient cellular differences in tissue remodelling capacity. Remodelling was induced by removing the outermost micro-posts, and micro-tissue compaction over time was assessed using transmitted light microscopy. Protein expression of tendon marker tenomodulin and myofibroblast marker α-smooth muscle actin (αSMA) were measured using Western blot. Expression and activity of remodelling marker MMP2 were determined using gelatin zymography. Cells were obtained from 12 patients (aged 12–51 years). Patient-specific variations in micro-tissue compaction speed or magnitude were observed. Up to 50-fold differences in αSMA expression were found between patients, although these did not correlate with faster or stronger compaction. Surprisingly, tenomodulin was only detected in samples obtained from two patients. Total MMP2 expression varied between patients, but no large differences in active fractions were found. No correlation of patient age with any of the remodelling-related factors was detected. Remodelling-related biological differences between patient tendon-derived cells could be assessed with the presented micro-tissue platform, and did not correlate with age. This demonstrates the need to compare this biological variation in vitro - especially cells with extreme properties - to clinical outcome. Sample size is currently increased, and patient outcome will be determined. Combined with results obtained from the in vitro platform, this could lead to a predictive tool to identify patients at risk for graft rupture

Used routinely in maxillofacial reconstructive surgery, the chondrocostal graft is also applied to hand surgery in traumatic or pathologic indications. The purpose of this overview was to analyze at long-term follow-up the radiological and histological evolution of this autograft, in hand and wrist surgery. We extrapolated this autograft technique to the elbow by using perichondrium. Since 1992, 148 patients have undergone chondrocostal autograft: 116 osteoarthritis of the thumb carpometacarpal joint, 18 radioscaphoid arthritis, 6 articular malunions of the distal radius, 4 kienbock's disease, and 4 traumatic loss of cartilage of the proximal interphalangeal (PIP) joint. Perichondrium autografts were used in 3 patients with elbow osteoarthritis. Magnetic Resonance Imaging (MRI) was performed in 19 patients with a mean follow-up of 68 months (4–159). Histological studies were performed on: i) perioperative chondrocostal grafts (n=3), ii) chondrocostal grafts explanted between 2 and 48 months after surgery (n=10), and iii) perioperative perichondrium grafts (n=2). Whatever the indication, the reconstruction by a chondrocostal/ostochondrocostal or perichondrium graft yielded satisfactory clinical results at long-term follow-up. The main question was the viability of the graft. -. For rib cartilage grafting: The radiological study indicated the non-wear of the graft and a certain degree of ossification. The MRI and histology confirmed a very small degree of osseous metaplasia and graft viability. The biopsies showed neo-vascularization of the cartilage that had undergone morphological, constitutional and architectural changes. Comparison of these structural modifications with perioperative chondrocostal graft histology is in progress. -. For perichondrium grafting: The first cases gave satisfactory clinical results but must be confirmed on a larger number of patients. Histological results highlighted a tissue composed of one fibrous layer and one cartilage-like layer, a common composition of supporting tissue. Despite the strong mechanical strain in the hand and wrist, chondrocostal graft is a biological arthroplasty that is trustworthy and secure over the long term, although it can cause infrequent complications inherent to this type of surgery. Despite the inevitable histological modification, the cartilage remains alive and is of satisfactory quality at long term follow-up and fulfills the requirements for interposition and reconstruction of an articular surface. The perichondrium graft constitutes a new arsenal to cure cartilage resurfacing. The importance of perichondrium for the survival of the grafted cartilage, as previously reported, as well as its role in resurfacing, is being investigated

The purpose of this anatomical study was to explore the morphological variations of the semitendinosus and gracilis tendons in length and cross-section and the statistical relationship between length, cross-section, and body height. We studied the legs of 93 humans in 136 cadavers. In 43 specimens (46.2%) it was possible to harvest the tendons from both legs. We found considerable differences in the length and cross-section of the semitendinosus and the gracilis tendons with a significant correlation between the two. A correlation between the length of the femur, reflecting height, and the length of the tendons was only observed in specimens harvested from women. The reason for this gender difference was unclear. Additionally, there was a correlation between the cross-sectional area of the tendons and the length of the femur. Surgeons should be aware of the possibility of encountering insufficient length of tendon when undertaking reconstructive surgery as a result of anatomical variations between patients

Summary Statement. Preoperative bone-marrow-derived cell mobilization by G-CSF is a safe orthopaedic procedure and allows circulation in the blood of high numbers of CD34+ve cells, promoting osseointegration of a bone substitute. Introduction. Granulocyte-colony-stimulating-factor(G-CSF) has been used to improve repair processes in different clinical settings for its role in bone-marrow stem cell(CD34+ and CD34-) mobilization. Recent literature suggests that G-CSF may also play a role in skeletal-tissue repair processes. Aim of the study was to verify the feasibility and safety of preoperative bone-marrow cell (BMC) mobilization by G-CSF in orthopaedic patients and to evaluate G-CSF efficacy in accelerating bone regeneration following opening-wedge high tibial valgus osteotomy(HTVO) for genu varum. Patients/Methods. 24 patients were enrolled in a prospective phase II trial. The osteotomy gap was filled by a hydroxyapatite-tricalciumphosphate bone substitute(HATriC). Patients were randomised to receive (GROUP A) or not receive (GROUP B) preoperatively a daily dose of 10µg/kg of G-CSF for three consecutive days, with an additional dose 4 hours before surgery. BMC-mobilization was monitored by white blood cell (WBC)-count, flow-cytometry analysis of circulating CD34+cells and Colony-forming cell assays. Patients were evaluated by: Lysholm and SF-36 scores preoperatively and at 1, 2, 3, 6, and 12 months after surgery;. X-ray evaluation preoperatively and at 1, 2, 3, 6, and 12 months after surgery, in order to compare the percentage of osseointegration of the bone-graft junction using the semi-quantitative score of Dallari[1]. CT-scan of the host bone-substitute interface at 2 months, in order to estimate the quality of the newly formed bone at the bone-graft junction by a quantitative measure of bone density (by Hounsfield unit) at the proximal and distal bone-graft junctions. Results. All patients completed the treatment program without major side effects; G-CSF was well tolerated. BMC-mobilization occurred in all Group A patients, with median peak values of 110/µL (range 29–256) of circulating CD34+ve cells. Circulating clonogenic progenitors paralleled CD34+ve cell levels. A significant improvement in the SF-36-Role-Physical scale and in the Lysholm score was recorded at follow-up in Group A compared to Group B(p<0.05). At the X-ray-evaluation, there was a significant increase in osseointegration at the bone-graft junction in Group A at 1, 2, 3 and 6 months post-surgery compared to Group B(p<0.05). CT-scans of the grafted area at 2 months post-surgery showed no significant difference in the quality of the newly formed bone between the two Groups. Discussion/Conclusions. These results suggest that G-CSF can be safely administered preoperatively in subjects undergoing HTVO. In addition, the clinical, radiographic and CT monitoring indicate that preoperative G-CSF administration promotes bone graft substitute osseointegration. Enhanced osseointegration might be the result of the direct activity of G-CSF on the host bone or a cellular effect mediated by bone marrow-derived progenitors mobilised by G-CSF, or by a combination of all these factors. This study is a proof-of-principle that preoperative G-CSF might be an alternative treatment option to enhance bone regeneration in the field of bone marrow stem cell therapy and reconstructive orthopaedic surgery

Background, Context and Motivation. “Increases in reconstructive orthopaedic surgery, resulting from advances in surgical practice and the ageing population, have lead to a demand for bone graft that far exceeds supply.”…Traditional bone grafting methods have been linked with a number of negative issues including increased morbidity due to secondary operation site and action as a vector for spread of disease. (Hing 2004). A solution to these insufficiencies would be the creation of a synthetic osteoinductive bone graft material. This would vastly improve bone graft surgery success rates and expedite post-op recovery times. The aim of this study was to classify then explore the dissolution rates of three experimental hydroxyapatite/silicate apatite synthetic bonegrafts in physiological solutions, (phosphate buffered saline, (PBS) +/− serum proteins, (PBS +FCS). The overall objective being to identify whether there is an explainable significant difference in ion exchange that could be behind the osteoinductive phenomena. Methods Used. Classification of the apatite samples, (HA, SA1 and SA2), was conducted via X-Ray diffraction, FTIR-PAS Spectroscopy and SEM with EDS analysis. A dissolution experiment of the experimental apatites was conducted in PBS and PBS + FCS solutions, over time periods of 1, 2 and 4 hours, and at 1, 2, 4 and 8 days, with repeat measures. Results and Conclusions. Silicon both free in solution and at the apatite surface was found to be key for osteoinduction and its presence at both these sites increases the rates of bone apposition around a synthetic graft. Experimental Samples HA, SA1 and SA2 share the same crystalline structure as Hydroxyapatite and are phase pure. Sample SA1 showed a %wt of silicon of 0.9%wt and SA2 showed a %wt of silicon of 0.6% wt. Review of the literature indicates that samples SA1 and SA2 are within an osteoinductive range for %wt of silicon. All three samples exhibit porosity within the most bioactive levels (150-500μm). Dissolution reactions for silicon are present and faster than experienced in the literature, this leads us to hypothesise that bone apposition rates would be high in all samples as silicon is available both free in solution and at the apatite surface, indicating all experimental samples possess an osteoinductive effect. Further work would involve exposing these samples to solutions containing osteoblast like cells and comparing the levels of activity found to those of traditional bone grafts currently used

Objectives

We sought to determine if a durable bilayer implant composed of trabecular metal with autologous periosteum on top would be suitable to reconstitute large osteochondral defects. This design would allow for secure implant fixation, subsequent integration and remodeling.

Trauma and orthopaedics is the largest of the surgical specialties and yet attracts a disproportionately small fraction of available national and international funding for health research. With the burden of musculoskeletal disease increasing, high-quality research is required to improve the evidence base for orthopaedic practice. Using the current research landscape in the United Kingdom as an example, but also addressing the international perspective, we highlight the issues surrounding poor levels of research funding in trauma and orthopaedics and indicate avenues for improving the impact and success of surgical musculoskeletal research.

Cite this article: Bone Joint J 2014; 96-B:1578–85.

Objectives

The period of post-operative treatment before surgical wounds are completely closed remains a key window, during which one can apply new technologies that can minimise complications. One such technology is the use of negative pressure wound therapy to manage and accelerate healing of the closed incisional wound (incisional NPWT).

The aim of this study was to determine whether exposure of human articular cartilage to hyperosmotic saline (0.9%, 600 mOsm) reduces in situ chondrocyte death following a standardised mechanical injury produced by a scalpel cut compared with the same assault and exposure to normal saline (0.9%, 285 mOsm). Human cartilage explants were exposed to normal (control) and hyperosmotic 0.9% saline solutions for five minutes before the mechanical injury to allow in situ chondrocytes to respond to the altered osmotic environment, and incubated for a further 2.5 hours in the same solutions following the mechanical injury.

Using confocal laser scanning microscopy, we identified a sixfold (p = 0.04) decrease in chondrocyte death following mechanical injury in the superficial zone of human articular cartilage exposed to hyperosmotic saline compared with normal saline.

These data suggest that increasing the osmolarity of joint irrigation solutions used during open and arthroscopic articular surgery may reduce chondrocyte death from surgical injury and could promote integrative cartilage repair.

Human bone-marrow mesenchymal stem cells have an important role in the repair of musculoskeletal tissues by migrating from the bone marrow into the injured site and undergoing differentiation. We investigated the use of autologous human serum as a substitute for fetal bovine serum in the ex vivo expansion medium to avoid the transmission of dangerous transfectants during clinical reconstruction procedures.

Autologous human serum was as effective in stimulating growth of bone-marrow stem cells as fetal bovine serum. Furthermore, medium supplemented with autologous human serum was more effective in promoting motility than medium with fetal bovine serum in all cases. Addition of B-fibroblast growth factor to medium with human serum stimulated growth, but not motility. Our results suggest that autologous human serum may provide sufficient ex vivo expansion of human bone-marrow mesenchymal stem cells possessing multidifferentiation potential and may be better than fetal bovine serum in preserving high motility.

In a study on ten fresh human cadavers we examined the change in the height of the intervertebral disc space, the angle of lordosis and the geometry of the facet joints after insertion of intervertebral total disc replacements. SB III Charité prostheses were inserted at L3-4, L4-5, and L5-S1. The changes studied were measured using computer navigation sofware applied to CT scans before and after instrumentation.

After disc replacement the mean lumbar disc height was doubled (p < 0.001). The mean angle of lordosis and the facet joint space increased by a statistically significant extent (p < 0.005 and p = 0.006, respectively). By contrast, the mean facet joint overlap was significantly reduced (p < 0.001). Our study indicates that the increase in the intervertebral disc height after disc replacement changes the geometry at the facet joints. This may have clinical relevance.

In a rabbit model we investigated the efficacy of a silk fibroin/hydroxyapatite (SF/HA) composite on the repair of a segmental bone defect. Four types of porous SF/HA composites (SF/HA-1, SF/HA-2, SF/HA-3, SF/HA-4) with different material ratios, pore sizes, porosity and additives were implanted subcutaneously into Sprague-Dawley rats to observe biodegradation. SF/HA-3, which had characteristics more suitable for a bone substitite based on strength and resorption was selected as a scaffold and co-cultured with rabbit bone-marrow stromal cells (BMSCs). A segmental bone defect was created in the rabbit radius. The animals were randomised into group 1 (SF/HA-3 combined with BMSCs implanted into the bone defect), group 2 (SF/HA implanted alone) and group 3 (nothing implanted). They were killed at four, eight and 12 weeks for visual, radiological and histological study.

The bone defects had complete union for group 1 and partial union in group 2, 12 weeks after operation. There was no formation of new bone in group 3. We conclude that SF/HA-3 combined with BMSCs supports bone healing and offers potential as a bone-graft substitute.