The purpose of this study was to develop a quality appraisal tool for the assessment of laboratory basic science biomechanical studies. Materials andScore development comprised of the following phases: item identification/development, item reduction, content/face/criterion validity, weighting, test-retest reliability and internal consistency. For item identification/development, the panel was asked to independently list criteria and factors they considered important for cadaver study and generate items that should be used to appraise cadaver study quality. For content validity, the content validity ratio (CVR) was calculated. The minimum accepted content validity index (CVI) was set to 0.85. For weighting, equal weight for each item was 6.7% [15 items]. Based on these figures the panel was asked to either upscale or downscale the weight for each item ensuring that the final sum for all items was 100%. Face validity was assessed by each panel member using a Likert scale from 1–7. Strong face validity was defined as a mean score of >5. Test-retest reliability was assessed using 10 randomly selected studies. Criterion validity was assessed using the QUACS scale as standard. Internal consistency was assessed using Cronbach's alpha. Five items reached a CVI of 1 and 10 items a CVI of 0.875. For weighting five items reached a final weight of 10% and ten items 5%. The mean score for face validity was 5.6. Test-retest reliability ranged from 0.78–1.00 with 9 items reaching a perfect score. Criterion validity was 0.76 and considered to be strong. Cronbach's alpha was calculated to be 0.71 indicating acceptable internal consistency. The new proposed quality score for basic science studies consists of 15 items and has been shown to be reliable, valid and of acceptable internal consistency. It is suggested that this score should be utilised when assessing basic science studies

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

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.

Injury to the anterior cruciate ligament (ACL) is one of the most devastating and frequent injuries of the knee. Surgical reconstruction is the current standard of care for treatment of ACL injuries in active patients. The widespread adoption of ACL reconstruction over primary repair was based on early perception of the limited healing capacity of the ACL. Although the majority of ACL reconstruction surgeries successfully restore gross joint stability, post-traumatic osteoarthritis is commonplace following these injuries, even with ACL reconstruction. The development of new techniques to limit the long-term clinical sequelae associated with ACL reconstruction has been the main focus of research over the past decades. The improved knowledge of healing, along with recent advances in tissue engineering and regenerative medicine, has resulted in the discovery of novel biologically augmented ACL-repair techniques that have satisfactory outcomes in preclinical studies. This instructional review provides a summary of the latest advances made in ACL repair.

Cite this article: Bone Joint Res 2014;3:20–31.

Abstract. Objectives. Review the evidence of low intensity pulsed ultrasound (LIPUS) for fracture non-union treatment and the potential to treat fractures in patients with co-morbidities at risk of fracture non-union. Methods. Data was gathered from both animal and human studies of fracture repair to provide an overview of the LIPUS in bone healing applications to provide in-depth evidence to substantiate the use in treatment of non-union fractures and to propose a scientific rational to develop a clinical development programme. Results. LIPUS is an effective method for treating fracture non-union, with most studies showing heal rates in the mid 80%. In the UK NICE has published MTG-12 guidance for non-union treatment, which demonstrates that LIPUS is an effective and cost effective method as an alternative to surgery to treat non-union fractures. Basic science studies and evaluation of clinical trial data has led to the understanding that LIPUS can mitigate co-morbidities related to failure of bone healing such as diabetes, advancing age and tobacco use. Future clinical trials will evaluate the use of LIPUS in acute fractures in patients with high risk of low bone healing capacity to prevent the development of a non-union. As with all medical treatments, LIPUS for fracture repair needs to be used appropriately, with poorly fixed fractures or large fracture gaps, being unsuitable for LIPUS treatment. In addition, considerations such as targeting the fracture site in deep-seated bones and clinician / patient engagement to ensure good compliant usage are vital factors to ensure good clinical outcomes. Conclusion. Using basic science research, a thorough knowledge of the mechanism of action has been established, which has elucidated that co-morbidities related to the development of fracture non-union can be mitigated by the LIPUS technology. A pragmatic clinical trial in the United States is currently ongoing to test these hypothesises clinically. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

Disease modifying approaches are commonly applied in OA patients. An aging society with better life expectancies is increasing in Europe and the globe. Orthobiologics cover intraarticular hyaluronan injections and also cellular therapies. Cellular therapies range from platelet rich plasma (PRP) applications to exosomes. Short term follow-up of limited number of patients revealed favorable results in clinical cellular therapies. Most of these studies evaluated decrease of pain and increase in function. Recent basic science studies focused on the action mechanism of orthobiologic therapies however patient perspective is less studied. Our research team has recently performed a qualitative study on the patient perspective of hyaluronan injection of the knee joint. Findings of that study will be shared and future patient knowledge based options on orthobiologics will be discussed

Abstract. INTRODUCTION. To preserve knee function and reduce degenerative, meniscal tears should be repaired where possible. Meniscal wrapping with collagen matrices has shown promising clinical outcome (AAOS meniscal algorithm), however there is limited basic science to support this. AIM. to model the contact pressures on the human tibial plateau beneath a (1) a repaired radial meniscal tear and (2) a wrapped and repaired radial meniscal tear. METHODOLOGY. Complete anterolateral radial tears were formed across 4 lateral human menisci, before repairing with ‘rip-stop’ H sutures using 2mm Arthrex Meniscal Suture tape. This was then repeated with the addition of a ChondroGide collagen matrix wrapping. From this experimental setup a finite element (FE) analysis model was construted. FE models of the two techniques (i) suture alone and (ii) suture and collagen-matrix wrap, were then modelled; bone was linear elastic, articular cartilage was a hyperelastic Yeoh model, and a linear elastic and transversely isotropic material model for the meniscus. The contact areas of the articulating surfaces, meniscus kinematics, and stress distribution around the repair were compared between the two systems. RESULTS. Meniscal suture-tape repair had higher local stresses and strains (σ_max=51 MPa ε_max=25%) around the repair compared to with Collagen wrapping (σ_max=36.6MPa ε_max=15%). Radial displacement and pressure on the meniscal contact surfaces were higher in the suture only repair. CONCLUSION. Collagen-matrix wrapping strengthens the repair, reducing local peak stresses and strains around the suture-tape. This could reduce the chance of suture-tape pull-out and subsequent repair failure

Glutamate regulates the expression of apoptosis-related genes and triggers the apoptosis of fibroblasts in rotator cuff tendons. Subacromial bursitis is always accompanied by symptomatic rotator cuff tear (RCT). However, no study has been reported on the presence of glutamate in subacromial bursa and on its involvement of shoulder pain in patients who had RCT. The purposes of this study were to determine whether the glutamate expression in subacromial bursa is associated with the presence of RCT and with the severity of shoulder pain accompanying RCT. Subacromial bursal tissues were harvested from patients who underwent arthroscopic rotator cuff tendon repair or glenoid labral repair with intact rotator cuff tendon. Glutamate tissue concentrations were measured, using a glutamate assay kit. Expressions of glutamate and its receptors in subacromial bursae were histologically determined. The sizes of RCT were determined by arthroscopic findings, using the DeOrio and Cofield classification. The severity of shoulder pain was determined, using visual analog scale (VAS). Any associations between glutamate concentrations and the size of RCT were evaluated, using logistic regression analysis. The correlation between glutamate concentrations and the severity of pain was determined, using the Pearson correlation coefficient. Differences with a probability <0.05 were considered statistically significant. Glutamate concentrations showed significant differences between the torn tendon group and the intact tendon group (P = 0.009). Concentrations of glutamate significantly increased according to increases in tear size (P < 0.001). In histological studies, the expressions of glutamate and of its ionotropic and metabotropic receptors have been confirmed in subacromial bursa. Glutamate concentrations were significantly correlated with pain on VAS (Rho=0.56 and P =0.01). The expression of glutamate in subacromial bursa is significantly associated with the presence of RCT and significantly correlated with its accompanying shoulder pain. Acknowledgements: This research was supported by the Basic Science Research Program, through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2015R1D1A3A01018955 and 2017R1D1A1B03035232)

Independent reviewers performed systematic reviews of the abstracts presented at the annual meeting of the ISSLS and the CSS. Papers employing blinded or independent review of outcome were the strongest predictor of publication and papers employing this had an adjusted odds ratio of 4.7 for being published compared to those papers that did not. Other significant factors include use of an experimental design, statistically positive result, and basic science research. To identify factors associated with eventual peer-reviewed publication in spinal research presented at national and international meetings. This review has highlighted factors that are associated with eventual peer-reviewed publication. It will also present comparisons between the International Society for Study of the Lumbar Spine (ISSLS) and the Canadian Spine Society (CSS). Independent reviewers performed systematic reviews of the abstracts presented at the annual meeting of the ISSLS and the CSS. All abstracts reviewed were categorized into type of research and aspects of research quality were identified. A medline database, blinded to the results of the review, was performed to identify abstracts that went onto peer-reviewed publication. Univariate and multivariate analyses reviewed that blinding, use of an experimental design, basic science or biomechanical research, and a statistically significant positive result were significant predictors of eventual publication. Papers employing blinded or independent review of outcome were the strongest predictor of publication and papers employing this had an adjusted odds ratio of 4.7 for being published compared to those papers that did not. Other significant factors include use of an experimental design, statistically positive result, and basic science research. Overall, 23% of ISSLS’ abstracts were published within one year and 67% within two years. In contrast, 6% and 13% of CSS abstracts were published within one and two years respectively

Aim. The coronavirus disease 2019 (COVID-19) pandemic presents significant challenges to healthcare systems globally. Orthopaedic surgeons are at risk of contracting COVID-19 due to their close contact with patients in both outpatient and theatre environments. The aim of this review was to perform a literature review, including articles of other coronaviruses, to formulate guidelines for orthopaedic healthcare staff. Methods. A search of Medline, EMBASE, the Cochrane Library, World Health Organization (WHO), and Centers for Disease Control and Prevention (CDC) databases was performed encompassing a variety of terms including ‘coronavirus’, ‘covid-19’, ‘orthopaedic’, ‘personal protective environment’ and ‘PPE’. Online database searches identified 354 articles. Articles were included if they studied any of the other coronaviruses or if the basic science could potentially applied to COVID-19 (i.e. use of an inactivated virus with a similar diameter to COVID-19). Two reviewers independently identified and screened articles based on the titles and abstracts. 274 were subsequently excluded, with 80 full-text articles retrieved and assessed for eligibility. Of these, 66 were excluded as they compared personal protection equipment to no personal protection equipment or referred to prevention measures in the context of bacterial infections. Results. There is a paucity of high quality evidence surrounding COVID-19. This review collates evidence from previous coronavirus outbreaks to put forward recommendations for orthopaedic surgeons during the COVID-19 pandemic. The key findings have been summarized and interpreted for application to the orthopaedic operative setting. Conclusion. For COVID-19 positive patients, minimum suggested PPE includes N95 respirator, goggles, face shield, gown, double gloves, and surgical balaclava. Space suits not advised. Be trained in the correct technique of donning and doffing PPE. Use negative pressure theatres if available. Minimize aerosolization and its effects (smoke evacuation and no pulse lavage). Minimize further unnecessary patient-staff contact (dissolvable sutures, clear dressings, split casts)

To analyse procedural details - specifically vertebral levels treated and injected polymethylmethacrylate (PMMA) volumes - of the publications by Buchbinder et al. . 1. and Kallmes et al. . 2. in the context of best available basic science. Review. Two randomised controlled trials published by the New England Journal of Medicine (NEJM) in 2009 comparing vertebroplasty to sham procedures conclude vertebroplasty to be no more effective than injection of local anaesthetic. This finding contradicts previous publications showing clinical efficacy. Neither investigation provides a breakdown of vertebral levels treated (original publication and supplementary material). Only one investigation provides information on fill volumes with average of 2.8 ml +/− 1.2 ml SD. The available basic science indicates a minimum fill volume of 13-16% of the vertebral body volume to be necessary for a relevant biomechanical effect on restoration of vertebral strength, according to which only vertebrae of the upper to mid thoracic spine could reasonably have received a biomechanically effective fill with the declared average volume of 2.8 ml +/− 1.2 ml SD. The available data of the NEJM publications strongly indicates that the treatment arm includes insufficiently treated patients. The technical information provided by the NEJM publications is insufficient to conclusively prove or disprove the clinical efficacy of vertebroplasty

The contents of 3 orthopaedic journals [JBJS (Am), JBJS (Br) and CORR] during 2001 and 2011 were compared for publication bias. There were total of 2028 articles. After exclusion 1662 scientific articles were analysed for statistical results, clinical conclusion, sub-speciality topics studied, the geographical region the study been conducted and the statistical method used. The articles classified into 7 categories: THR, TKR, Basic sciences, Trauma, Spinal disorders, Paediatric disorders and Tumour. 91% of articles on THR and 95% of articles on TKR were positive studies in 2001. Articles dealing with trauma had the lowest proportion of positive studies (74%) as compared to all other topics. We noted that JBJS (Br) published more negative studies as compared to JBJS (Am) and CORR. In 2011 less articles on THR and TKR had positive studies (68% and 76% respectively). Spinal surgery articles report less number of non significant studies nowadays (24% in 2001 and 2% in 2011). There is a significant change in the trend towards reporting more negative studies in relation with THR and TKR (p < 0.05). Articles dealing with Basic sciences, Trauma, Paediatric disorders and Tumour did not have any significant change in reporting negative studies in the last decade. Significant findings in spinal disorders were 3.8 times more likely to be published than non significant stdies. Overall, JBJS (Br) continued to publish more negative studies as compared to JBJS (Am) and CORR. Journals seem to prefer reporting more significant results with spinal disorders and more non significant results in relation with Hip and Knee arthroplasty in last ten years. This might be because of authors' perceptions of the importance of their findings and journals preferences for significant results

Background. The rate of subsidence for lumbar fusion surgery is variable from 7- 89%. Subsidance can affect the outcome of surgery by compramising alignment, foraminal height and stability. Modic changes have been shown to affect the stiffness and strength of the vertebral end plate and shown to affect both fusion rates and clinical outcome. Ongoing laboratory investigations into the material properties of the degenerate lumbar spine show modic changes affect the end plate and trabecular bone mechanics. This study aims to bridge this basic science research into clinical practice. Methods. A retrospective analysis of all patients in two tertiary spinal centres who have undergone lumbar interbody fusion with the implantation of a ‘cage’ over the past 6 years were analysed by two independent spinal surgeons. Pre-operative MRI findings were correlated with post-operative interbody cage subsidence after 1 year. Results. A total of 108 Interbody cages were included. Comparison of demographics did not reveal and significant between group variations. Comparison made between those displaying no modic changes and those displaying any of the three modic change types revealed a significantly higher subsidence rate in those displaying modic changes (p=0.003). Subgroup analysis showed that Type 2 modic changes (n=27) had a significantly higher subsidence rate (p=0.002). Those displaying type 3 modic changes (n=7) did not have any incidents of subsidence. Conclusions. Type 2 modic changes are associated with a higher rate of Lumbar interbody cage subsidence in this study. Those displaying type 3 changes seem to be protected from interbody cage subsidence. No Conflict of Interest. Funding: Produced as part of a research grant from the Gwen Fish Trust and Action Arthritis

Distal radius fractures (DRF) are the most common fracture type in all age groups combined. Unstable DRF may be surgically managed with volar or dorsal plate fixation. Dorsal plating has traditionally been associated with decreased range of motion (ROM). However, this assumption has not been recently assessed to determine whether functional ROM is achievable (approximately 54 degrees of flexion and 60 degrees of extension) with recent advances in lower profile dorsal plate design. The aim of this study was therefore to compare ROM and patient reported outcome measures between volar and dorsal plating methods for DRF. A meta-analysis was performed to directly compare ROM and Disabilities of Arm, Shoulder and Hand (DASH) scores between dorsal and volar plate fixation for DRF. Separate literature searches for each plating method were performed using MedLine and EMBase on January 28, 2018. Exclusion criteria consisted of non-English articles, basic science articles, animal/cadaver studies, case studies/series, combined operative approaches, papers published more than 20 years ago and paediatric studies. Only articles with at least one year patient follow-up and a) ROM and AO-OTA distal radius fracture classification, or b) DASH scores were included. Raw data was extracted from all articles that met inclusion criteria to compile a comprehensive dataset for analysis. Descriptive statistics with z-score comparison for AO-OTA classification or a two-tailed independent samples t-tests for ROM and DASH scores for dorsal versus volar plating were performed. Significance was defined as p < 0 .05. After rigorous screening, six dorsal plating and 43 volar plating articles met inclusion criteria for ROM/AO-OTA classification versus six dorsal plating and 44 volar plating articles for DASH scores. The weighted means of flexion (dorsal 54.9 degrees, SD 9.3, n=257, volar 61.3 degrees, SD 11.5, n=1906) and extension (dorsal 60 degrees, SD 12, n=257, volar 62.8 degrees, SD 11.4, n=1906) were significantly different (both p < 0 .001) between the two plating methods. The volar plating group had a significantly higher proportion of type C fractures (dorsal 0.5, n =169, volar 0.6, n=1246, p < 0 .001). The weighted means of reported DASH scores were not significantly different between dorsal (14, SD 14.8) versus volar (13.6, SD 12.8) plating (p=0.54). Though mean wrist flexion and extension were statistically different between the dorsal versus volar plating methods, the difference between group means was less than 5-degrees, which is unlikely to be clinically significant. Additionally, there was no significant difference in DASH scores between the two plating methods. Taken together, these findings imply that the statistical difference in ROM outcomes are likely not clinically significant and should therefore not dictate choice of plating method for fixation of DRF

Distal radius fractures (DRF) are the most common fracture type in all age groups combined. Unstable DRF may be surgically managed with volar or dorsal plate fixation. Dorsal plating has traditionally been associated with decreased range of motion (ROM). However, this assumption has not been recently assessed to determine whether functional ROM is achievable (approximately 54o of flexion and 60o of extension) with recent advances in lower profile dorsal plate design. The aim of this study was therefore to compare ROM and patient reported outcome measures between volar and dorsal plating methods for DRF. A meta-analysis was performed to directly compare ROM and DASH scores between dorsal and volar plate fixation for DRF. Separate literature searches for each plating method were performed using MedLine and EMBase on January 28, 2018. Exclusion criteria consisted of non-English articles, basic science articles, animal/cadaver studies, case studies/series, combined operative approaches, papers published more than 20 years ago and paediatric studies. Only articles with at least one year patient follow-up and a) ROM and AO distal radius fracture classification, or b) DASH scores were included. Raw data was extracted from all articles that met inclusion criteria to compile a comprehensive dataset for analysis. Descriptive statistics with z-score comparison for AO classification or a two-tailed independent samples t-test for ROM and DASH scores for dorsal versus volar plating were performed. Significance was defined as p < 0 .05. After rigorous screening, 6 dorsal plating and 43 volar plating articles met inclusion criteria for ROM/AO classification versus 6 dorsal plating and 44 volar plating articles for DASH scores. The weighted means of flexion (dorsal 54.9o, SD 9.3, n=257, volar 61.3o, SD 11.5, n=1906) and extension (dorsal 60.0o, SD 12, n=257, volar 62.8o, SD 11.4, n=1906) were statistically significantly different (both p < 0 .001) between the two plating methods. The volar plating group had a significantly higher proportion of AO type C fractures (dorsal 0.5, n =169, volar 0.6, n=1246, p < 0 .001). The weighted means of reported DASH scores were not significantly different between dorsal (14.01, SD 14.8) versus volar (13.6, SD 12.8) plating (p=0.54). Though mean wrist flexion and extension were statistically different between the dorsal versus volar plating methods, the difference between group means was less than 5o, which is unlikely to be clinically significant. Additionally, we did not find a significant difference in DASH scores between the two plating methods. Taken together, these findings imply that the statistical difference in ROM outcomes are likely not clinically significant and should therefore not dictate choice of plating method for fixation of DRF

Periprosthetic joint infection (PJI) is a devastating complication of total hip arthroplasty (THA). According to registry-based studies, some bearing couples are associated with an increased risk of PJI. The recent International Consensus on Periprosthetic Joint Infection stated that metal-on-metal (MOM) bearing surface appeared to be associated with a higher incidence of PJI. Based on emerging reports, the incidence of PJI appears to be different among different bearing surfaces. We conducted a multi-institutional study attempting to study this exact issue. The purpose of the study was to determine whether there was any difference in the incidence of PJI in two commonly used bearing couples (metal- on-polyethylene versus ceramic-on-polyethylene). Based on a retrospective multi-institutional query all patients who received primary THA with MOP or COP bearing surfaces performed during 2005–2009 in two high-volume arthroplasty centers were identified. Demographic factors, comorbidities, length of hospital stay, complications and other relevant information were extracted. PJI was defined based on the MSIS (International Consensus) criteria. Multivariate analysis was performed to determine whether bearing coupling was independently correlated with PJI. In our data, 25/2,921 (0.9%) patients with MOP and 11/2,643 (0.4%) patients with COP developed PJI. This difference was statistically significant (p=0.01). After the multivariate analysis, controlling for potential confounders (age, body mass index and length of hospital stay, Charlson comorbidity index), MOP bearing surface was found to be an independent factor correlating with higher incidence of PJI (odds ratio: 2.6, 95% confidence interval: 1.02–6.54, p=0.04). The finding of this study, and others from centers in Europe, suggest that the bearing surface may have an influence on the incidence of PJI. Although, we had originally thought that ceramic bearing surfaces may be used in younger and healthier patients, the multivariate analyses that controlled for all these variables confirms that use of metal femoral head is an independent risk factor for development of PJI. The finding of this study is compelling and begs for future basic science mechanistic investigations

Background. There are currently no effective treatments for skeletal muscle fibrosis. Myofibroblasts are the major cellular effectors of fibrosis but their origin in muscle is unknown. We report that PDGFRβ (platelet derived growth factor receptor beta) Cre inactivates genes in murine PDGFRβ+ cells and myofibroblasts in muscle with high efficiency. We used this system to delete the integrin αv subunit because of the suggested role of multiple αv integrins as central mediators of fibrosis in multiple organs. Methods. Muscle fibrosis was induced by intramuscular cardiotoxin (CTX) injection. The contribution of PDGFRβ+ cells to fibrosis was assessed in double-flourescent reporter (mTmG) mice under PDGFRβ-Cre control. Itgavflox/flox;PDGFRβ-Cre mice were used to investigate whether loss of αv integrins on PDGFRβ+ cells influences fibrosis development. A small-molecule inhibitor of αv integrins (CWHM12) was used to determine whether pharmacological blockade of αv integrins could attenuate fibrosis. Results. At 21 days following injury PDGFRβ+ cells in mTmG;PDGFRβ-Cre mice were distributed in a manner characteristic of myofibroblasts. PDGFRβ+ cells sorted from injured muscles of mTmG;PDGFRβ-Cre mice showed induction of genes associated with myofibroblastic transition. Itgavflox/flox;PDGFRβ-Cre mice were protected from CTX induced fibrosis, as determined by picrosirius red staining for collagen (p<0.01). Sorted and culture activated αv-null PDGFRβ+ cells demonstrated significant reduction in collagen1 over controls (p<0.05). CWHM12 significantly reduced muscle fibrosis when delivered from the time of injury (prophylactic model: p<0.01) and from day 10 post injury (therapeutic model: p<0.01). Furthermore, CWHM12 inhibited collagen1 expression by PDGFRβ+ cells ex-vivo (p<0.05). Conclusions. PDGFRβ-Cre labels profibrotic cells in skeletal muscle and depletion of αv integrins in these cells reduces muscle fibrosis. Most importantly from a treatment standpoint, pharmacologic inhibition of αv integrins using a small molecule inhibitor may have utility in the prevention and treatment of skeletal muscle fibrosis. Level of Evidence. Basic Science

Cartilage repair in terms of replacement, or regeneration of damaged or diseased articular cartilage with functional tissue, is the ‘holy grail’ of joint surgery. A wide spectrum of strategies for cartilage repair currently exists and several of these techniques have been reported to be associated with successful clinical outcomes for appropriately selected indications. However, based on respective advantages, disadvantages, and limitations, no single strategy, or even combination of strategies, provides surgeons with viable options for attaining successful long-term outcomes in the majority of patients. As such, development of novel techniques and optimisation of current techniques need to be, and are, the focus of a great deal of research from the basic science level to clinical trials. Translational research that bridges scientific discoveries to clinical application involves the use of animal models in order to assess safety and efficacy for regulatory approval for human use. This review article provides an overview of animal models for cartilage repair. Cite this article: Bone Joint Res 2014;4:89–94

The incorporation of platelet rich plasma (PRP) in the treatment of various musculoskeletal conditions has increased exponentially over the past decade. While described most often as an augment or treatment for tendinopathies and acute tendon injuries, more recently, PRP has been described as an adjunct to arthroplasty procedures, mostly with respect to knee arthroplasty. In the shoulder, only a single study has been published, in which Zavadil and colleagues performed a randomised study of 40 patients undergoing total shoulder arthroplasty undergoing either treatment with autologous platelet gel and platelet poor plasma (n=20) or undergoing no biologic treatment (control group, n=20). The authors noted that the treatment group had significantly lower pain scores, less pain medication requirements, and improved internal rotation when compared to controls; in addition, there were no significant differences in post-operative (compared to pre-operative) hemoglobin levels or length of stay. The vast majority of arthroplasty studies discussing PRP analyze the impact of treatment on wound healing, post-operative pain, post-operative range of motion, and need for post-operative blood transfusions. Unfortunately, due to the substantial variability of methodology (not all PRP preparations are the same) in the available studies as well as the variability in outcomes reporting, direct comparison between different studies is not feasible. Here, we discuss the basic science elements of PRP relevant to arthroplasty, the variability of PRP solutions, the specific applications of PRP in arthroplasty, and the latest clinical outcomes analyses of patients undergoing PRP therapy in conjunction with shoulder arthroplasty

Current dogma is that a programme of anatomic repositioning with rigid internal fixation of fractures will lead to successful healing. Failures are attributed to failures in technique, not in instruments, implants, or concepts. Current basic science research shows that in the osteoporotic skeleton, bone trabeculae, once lost, are not replaced. This is true in fractures. In a series of cases, the author will show that lost bone is indeed not replaced, and the unsuccessful clinical outcome is caused by adherence to concepts that do not solve the problem of fracture repair in the elderly. Five specific case examples will be shown to demonstrate this problem. Despite an abundance of bone graft substitutes, bone morphogenic protein preparations, and cancellous bone autografting, the problem of dependable fracture repair in the elderly skeleton still needs to be solved