Aims. After a few passages of in vitro culture, primary human articular chondrocytes undergo senescence and loss of their phenotype. Most of the available chondrocyte cell lines have been obtained from cartilage tissues different from diarthrodial joints, and their utility for osteoarthritis (OA) research is reduced. Thus, the goal of this research was the development of immortalized chondrocyte cell lines proceeded from the articular cartilage of patients with and without OA. Methods. Using telomerase reverse transcriptase (hTERT) and SV40 large T antigen (SV40LT), we transduced primary OA articular chondrocytes. Proliferative capacity, degree of senescence, and chondrocyte surface antigen expression in transduced chondrocytes were evaluated. In addition, the capacity of transduced chondrocytes to synthesize a tissue similar to cartilage and to respond to interleukin (IL)-1β was assessed. Results. Coexpression of both transgenes (SV40 and hTERT) were observed in the nuclei of transduced chondrocytes. Generated chondrocyte cell lines showed a high proliferation capacity and less than 2% of senescent cells. These cell lines were able to form 3D aggregates analogous to those generated by primary articular chondrocytes, but were unsuccessful in synthesizing cartilage-like tissue when seeded on type I collagen sponges. However, generated chondrocyte cell lines maintained the potential to respond to IL-1β stimulation. Conclusion. Through SV40LT and hTERT transduction, we successfully immortalized chondrocytes. These immortalized chondrocytes were able to overcome senescence in vitro, but were incapable of synthesizing cartilage-like tissue under the experimental conditions. Nonetheless, these chondrocyte cell lines could be advantageous for OA investigation since, similarly to primary articular chondrocytes, they showed capacity to upregulate inflammatory mediators in response to the IL-1β cytokine. Cite this article: Bone Joint Res 2023;12(1):46–57

Osteoarthritis (OA) is a disease of the synovial joint with synovial inflammation, capsular contracture, articular cartilage degradation, subchondral sclerosis and osteophyte formation contributing to pain and disability. Transcriptomic datasets have identified genetic loci in hip and knee OA demonstrating joint specificity. A limited number of studies have directly investigated transcriptional changes in shoulder OA. Further, gene expression patterns of periarticular tissues in OA have not been thoroughly investigated. This prospective case control series details transcriptomic expression of shoulder OA by analysing periarticular tissues in patients undergoing shoulder replacement for OA as correlated with a validated patient reported outcome measure of shoulder function, an increasing (clinically worsening) QuickDASH score. We then compared transcriptomic expression profiles in capsular tissue biopsies from the OA group (N=6) as compared to patients undergoing shoulder stabilisation for recurrent instability (the control group, N=26). Results indicated that top ranked genes associated with increasing QuickDASH score across all tissues involved inflammation and response to stress, namely interleukins, chemokines, complement components, nuclear response factors and immediate early response genes. Some of these genes were upregulated, and some downregulated, suggestive of a state of flux between inflammatory and anti-inflammatory signalling pathways. We have also described gene expression pathways in shoulder OA not previously identified in hip and knee OA, as well as novel genes involved in shoulder OA

Osteoarthritis (OA) is an inflammatory disease affecting the complete synovial joint including the cartilage layer and the subchondral bone plate. Due to the multifactorial causes and the not yet completely resolved molecular mechanisms, it lacks a gold standard treatment to mitigate OA. Hence, biomaterials capable of delaying or preventing OA are a promising alternative or supplement to antiphlogistic and surgical interventions. Magnesium (Mg) and its alloys are among the promising biomaterials with osteoinductive effects. This work investigated the impact of Mg micro cylinders (length ≈of 1.0 mm and width of 0.5 mm) in vitro, in favoring joint regeneration together with preventing OA progression. Therefore, a mesenchymal stem cell line (SCP-1) was applied in order to assess the compatibility of the degradable material. Furthermore, an in vitro OA model utilizing SCP-1 cells based on the supplementation of the cytokines; IL-1β, TNF-α was established and disclosed the capability of Mg microparticles in differentiating SCP-1 cells into chondrogenic and osteogenic lineages proven through extracellular matrix staining and gene marker analysis. A concentration above 10 mM revealed a reduction in the cell viability by 50 %. An increase in the expression of collagens especially and proteoglycans (COL2A1, Aggrecan) as extracellular matrix proteins as well as an increase in osteogenic marker (ALP, BMP2) favoring the mineralization process were observed. The inflammatory condition reduced the viability and productivity of the applied stem cell line. However, the application of Mg microparticles induced a cell recovery and reduction of inflammation marker such as MMP1 and IL6. The cytocompatible and the ability of Mg microparticles in supporting bone and cartilage repair mechanisms in vitro even under inflammatory conditions make biodegradable Mg microparticles a suitable implant material to treat OA therapy. Acknowledgements: This project OAMag was funded by the German Research Foundation (project number 404534760). The author thank Dr. Björn Wiese (hereon) for the production of Mg based material and Prof. Böcker (MUM Musculoskeletal University Center Munich) for the provision of SCP-1 cell line

Intervertebral disc degeneration is a common cause of low-back pain, the musculoskeletal disorder with the largest impact world-wide. The complex disease is however not yet well understood, and no treatment is available. This is somewhat in contrast with osteoarthritis, a subject of more extensive research. Intervertebral disc degeneration may though be a type of osteoarthritis, as other vertebrates have a diarthrodial joint instead of an intervertebral disc. We describe the parallel in view of the anatomy, composition and degeneration of the intervertebral disc and articular joint. Not only different embryonic origin and anatomy suggest significant differences between the intervertebral disc and the synovial joint, but their biomechanical properties also partly differ, as articulation is one of the key properties of a synovial joint and does not occur in the intervertebral disc. However, both tissues provide flexibility and are able to endure compressive loads, and both cell behavior and extracellular matrix appear much the same, mainly existing of chondrocytes, proteoglycans and collagen type II, suggesting that the environment of the cell is more important to its behavior than embryonic origin. Moreover, great similarities are found in the inflammatory cytokines, which are mainly IL-1β and TNF-α, and matrix-degrading factors (i.e. MMPs and ADAMTSs) involved in the cascade of degeneration, resulting in overlapping clinical and radiological features such as loss of joint space, subchondral sclerosis, and the formation of osteophytes, causing pain and morning stiffness. Therefore, we state that disc degeneration can result in the osteoarthritic intervertebral disc. This point of view may enhance the synergy between both fields of research, and potentially provide new regenerative strategies for intervertebral disc degeneration

Objectives. Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like joint damage in the shoulders, knees, and hips of rats after induction of obesity, and to identify potential joint-specific risks for OA-like changes. Methods. A total of 16 male Sprague-Dawley rats were allocated to either the diet-induced obesity group (DIO, 40% fat, 45% sucrose, n = 9) or a chow control diet (n = 7) for 12 weeks. At sacrifice, histological assessments of the shoulder, hip, and knee joints were performed. Serum inflammatory mediators and body composition were also evaluated. The total Mankin score for each animal was assessed by adding together the individual Modified Mankin scores across all three joints. Linear regression modelling was conducted to evaluate predictive relationships between serum mediators and total joint damage. Results. The HFS diet, in the absence of trauma, resulted in increased joint damage in the shoulder and knee joints of rats. Hip joint damage, however, was not significantly affected by DIO, consistent with findings in human studies. The total Mankin score was increased in DIO animals compared with the chow group, and was associated with percentage of body fat. Positive significant predictive relationships for total Mankin score were found between body fat and two serum mediators (interleukin 1 alpha (IL-1α) and vascular endothelial growth factor (VEGF)). Conclusion. Systemic inflammatory alterations from DIO in this model system may result in a higher risk for development of knee, shoulder, and multi-joint damage with a HFS diet. Cite this article: K. H. Collins, D. A. Hart, R. A. Seerattan, R. A. Reimer, W. Herzog. High-fat/high-sucrose diet-induced obesity results in joint-specific development of osteoarthritis-like degeneration in a rat model. Bone Joint Res 2018;7:274–281. DOI: 10.1302/2046-3758.74.BJR-2017-0201.R2

Objectives. We investigated the reliability of the cobalt-chromium (CoCr) synovial joint fluid ratio (JFR) in identifying the presence of a severe aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) response and/or suboptimal taper performance (SOTP) following metal-on-metal (MoM) hip arthroplasty. We then examined the possibility that the CoCr JFR may influence the serum partitioning of Co and Cr. Methods. For part A, we included all revision surgeries carried out at our unit with the relevant data, including volumetric wear analysis, joint fluid (JF) Co and Cr concentrations, and ALVAL grade (n = 315). Receiver operating characteristic curves were constructed to assess the reliability of the CoCr JFR in identifying severe ALVAL and/or SOTP. For part B, we included only patients with unilateral prostheses who had given matched serum and whole blood samples for Co and Cr analysis (n = 155). Multiple regression was used to examine the influence of JF concentrations on the serum partitioning of Co and Cr in the blood. Results. A CoCr JFR > 1 showed a specificity of 83% (77% to 88%) and sensitivity of 63% (55% to 70%) for the detection of severe ALVAL and/or SOTP. In patients with CoCr JFRs > 1, the median blood Cr to serum Cr ratio was 0.99, compared with 0.71 in patients with CoCr JFRs < 1 (p < 0.001). Regression analysis demonstrated that the blood Cr to serum Cr value was positively associated with the JF Co concentration (p = 0.011) and inversely related to the JF Cr concentration (p < 0.001). Conclusion. Elevations in CoCr JFRs are associated with adverse biological (severe ALVAL) or tribocorrosive processes (SOTP). Comparison of serum Cr with blood Cr concentrations may be a useful additional clinical tool to help to identify these conditions. Cite this article: D. J. Langton, S. Natu, C. F. Harrington, J. G. Bowsher, A. V. F. Nargol. Is the synovial fluid cobalt-to-chromium ratio related to the serum partitioning of metal debris following metal-on-metal hip arthroplasty? Bone Joint Res 2019;8:146–155. DOI: 10.1302/2046-3758.83.BJR-2018-0049.R1

Abstract. Objectives. Current use of hard biomaterials such as cobalt-chrome alloys or ceramics to articulate against the relatively soft, compliant native cartilage surface reduces the joint contact area by up to two thirds. This gives rise to high and abnormal loading conditions which promotes degradation and erosion of the mating cartilage leading to pain, stiffness, and loss of function. Biomimetic soft lubrication strategies have been developed by grafting hydrophilic polymers onto substrates to form a gel-type surface. Surface grafted gels mimic the natural mechanisms of friction dissipation in synovial joints, showing a promising potential for use in hemiarthroplasty. This project aims to develop implant surfaces with properties tailored to match articular cartilage to retain and promote natural joint function ahead of total joint replacement. Methods. Four different types of monomers were grafted in a one-step photopolymerisation procedure onto polished PEEK substrates. The functionalised surfaces were investigated using surface wettability, FTIR, and simplified 2D-tribometry tests against glass and animal cartilage specimens to assess their lubricity and mechanical properties for hemiarthroplasty articulations. Results. Polymer functionalised surfaces under different grafting conditions were assessed for their wettability, graft density and quality. A reduction in water contact angle from 90° to < 20° was seen for functionalised highly hydrophilic PEEK surfaces. Similarly a reduction in the coefficient of friction (and subsequently shear stresses acting on cartilage) of 95% to ∼ 10. −2. was seen for functionalised PEEK surfaces slid against glass and cartilage in PBS. Conclusions. Development of this technology has the potential to vastly improve the performance of hemiarthroplasty. Providing earlier and targeted interventions for degenerative joint disease whilst preserving the function of the remaining healthy cartilage. Future work will concern using these promising hydrated functionalised surface architectures as focal cartilage deflects plugs along with long-term performance and suitability for implantation assessments using joint simulator testing

Abstract. INTRODUCTION. Knee tactile afferents act as synovial joint limit detectors, eliciting signalling upon excessive fibrous tissue strain but play little role in joint function as disruption of their activity does not induce impairments in movement or sensation. In contrast, knee nociceptive afferents gain activity upon inflammation producing painful sensation in pathology such as osteoarthritis. We hypothesize that similar in origin, fast-conducting tactile afferents become sensitized by inflammatory mediators and gain activity causing proprioceptive sensation impairment in patients with knee pathology, driving gait abnormalities and osteoarthritis progression. To investigate the activity of these neurons, we will produce a co-culture model using our existing 3D bone mimetic and iPSC derived tactile sensory neurons by utilizing the NGN2-BRN3A plasmid produced by Nickolls et al producing a model of these tactile neurons at their position within the joint at the fibrous/bony interface. METHODS. Human Y201 MSC cells embedded in type I collagen gels (0.05 × 106 cell/gel) were differentiated to osteocytes andmechanically loaded in silicone plates (5000 µstrain, 10Hz, 3000 cycles) (n=5). RNA quantified by RNAseq analysis (NovaSeq S1) and neuronal communication pathways identified using DEseq2 analysis. RESULTS. Over 20 genes involved in neural communication were expressed in 100% of bone cultures, and most of these showed regulation under mechanical strain including receptors for Substance P (p= 0.91), CGRP (p=0.05), Norepinepherin (p=0.002), NPY (p=0.0002), Sema3A (p=0.01), Leptin (p=0.00005), Neutrophin3A (p=0.23), BDNF (p=0.5), GDNF (p=0.02), and glutamate(p=0.024) and signalling molecules Neutrophin3 (p=0.73), NGF (p=0.02), Sema3A (p=0.003), BDNF (p=0.02) and GDNF (p=0.006). DISCUSSION. The production of this 3D neural co-culture model is still in its infancy. However, preliminary RNAseq data has shown our Y201 bone model expresses all the signalling pathways known to exert neural regulatory responses and therefore is now ready to move forward to neural inclusion

Construction of a functional skeleton is accomplished through co-ordination of the developmental processes of chondrogenesis, osteogenesis, and synovial joint formation. Infants whose movement in utero is reduced or restricted and who subsequently suffer from joint dysplasia (including joint contractures) and thin hypo-mineralised bones, demonstrate that embryonic movement is crucial for appropriate skeletogenesis. This has been confirmed in mouse, chick, and zebrafish animal models, where reduced or eliminated movement consistently yields similar malformations and which provide the possibility of experimentation to uncover the precise disturbances and the mechanisms by which movement impacts molecular regulation. Molecular genetic studies have shown the important roles played by cell communication signalling pathways, namely Wnt, Hedgehog, and transforming growth factor-beta/bone morphogenetic protein. These pathways regulate cell behaviours such as proliferation and differentiation to control maturation of the skeletal elements, and are affected when movement is altered. Cell contacts to the extra-cellular matrix as well as the cytoskeleton offer a means of mechanotransduction which could integrate mechanical cues with genetic regulation. Indeed, expression of cytoskeletal genes has been shown to be affected by immobilisation. In addition to furthering our understanding of a fundamental aspect of cell control and differentiation during development, research in this area is applicable to the engineering of stable skeletal tissues from stem cells, which relies on an understanding of developmental mechanisms including genetic and physical criteria. A deeper understanding of how movement affects skeletogenesis therefore has broader implications for regenerative therapeutics for injury or disease, as well as for optimisation of physical therapy regimes for individuals affected by skeletal abnormalities. Cite this article: Bone Joint Res 2015;4:105–116

The reduction of both friction and wear is required in existing joint prostheses composed of ultra-high molecular weight polyethylene (UHMWPE) and metallic or ceramic components, or even in Hard-on-Hard joint prostheses. In contrast, the healthy natural synovial joints with rubbing surfaces of articular cartilage are likely to operate at very low friction and low wear for the entire lifetime in the adaptive multimode lubrication mechanism, in which various lubrication modes become effective in various daily activities. Therefore, to establish a similar lubrication mechanism in joint prostheses by the application of compliant artificial cartilage, we conduct various researches to improve lubrication modes resulting in reduction in both friction and wear. In this paper, the effectiveness of the hydrogel artificial cartilage of high water content is discussed from the viewpoint of bionic design to mimic natural synovial joints. The aim of this paper is to facilitate a function based on multimode lubrication mechanism in joint prostheses similar to natural synovial joints. Firstly, the possibility of full elastohydrodynamic lubrication was evaluated by experimental methods in friction tester and joint simulator. The joint prostheses with compliant rubbing materials or polymer-on-hard joint with better geometrical congruity showed siginificant fluid film formation, but some local intimate contact occurred. Therefore, as the second viewpoint, the effectiveness of adsorbed film formation was examined. The noteworthy phenomena are remarkable reduction in friction for artificial joint with poly(vinyl alcohol) (PVA) hydrogel articular surfaces and a notable increase in friction for artificial joint with polyurethane surface in hyaluronate solutions containing serum proteins. These results indicated that adsorbed protein films can reduce or increase friction and wear depending on probably fluid film thickness. Other findings of effectiveness of layered adsorbed film and negative effect of heterogeneous adsorbed film are described on the basis of various observation in friction tests. As the third viewpoint, the importance of biphasic lubrication and hydration lubrication for hydrogel surface with high water content is discussed. In friction tests of natural articular cartilage against glass plate, it was observed that the unloading for 5 min after continuous 30 min rubbing reduced the friction at restarting probably due to biphasic lubrication and/or hydration lubrication after rehydration, where adsorbed films have some influences on friction and wear. For joint prostheses with compliant hydrogel artificial cartilage, similar mechanism is required for surface and bulk structure of artificial cartilage. In this paper, several important essential points from the bionic design are indicated for development of the next generation for joint prostheses with higher function and better longevity

Gram staining is used as an initial indicator of synovial joint infection but has widely varied false negative rates in the literature. Clinical decisions are often made on the basis of gram stain results, such as whether a patient requires urgent surgery, and therefore it is important to understand the tests efficacy. A retrospective review of synovial fluid aspirates in NHS Tayside for the years 2017 and 2018 was performed from the departmental microbiology database. Aspirates of large joints were included (hip, knee, shoulder, wrist, elbow, ankle). Any joints with prosthesis were excluded, including fixation metalwork. Any abscess overlying a joint that was not proven to penetrate the joint was also excluded. Initial gram stain results and formal culture results were reviewed. Final culture results were considered to be the gold standard to compare gram stain results to. 2167 samples were reviewed. Of these 1552 were excluded base on inclusion criteria. Of the remaining 615, 120 (19.5%) were culture positive. There were 33 positive gram stain results, 1 false positive and 32 true positive results. The sensitivity was 26.67% with a specificity of 99.80% (p=0.0001). The negative predictive value is 84.88% (CI 83.44% – 86.21%). These results show that gram stain tests of native joints have a low sensitivity and poor negative predictive value. This is reflected in the current literature with prosthetic joints. Based on this study caution should be used when interpreting a negative gram stain result with appropriate safety netting and follow up required alongside clinical assessment

The avascular nature of articular cartilage relies on diffusion pathways to obtain essential nutrients and molecules for cellular activity. Understanding these transport pathways is essential to maintaining and improving the health of articular cartilage and ultimately synovial joints. Several studies have shown that joint articulation is associated with fluid and solute uptake although it remains unclear what role sliding motion independently plays. This study investigates the role of sliding with a non-stationary contact area on the uptake of small molecular weight tracers into articular cartilage. Ten-millimeter diameter cartilage-bone plugs were obtained from porcine knee joints and sealed into purpose made diffusion chambers. The chambers were designed to eliminate diffusion from the radial edge and only allow diffusion through the articular surface. The bone side of the chamber was filled with PBS to maintain tissue hydration while the cartilage side was filled with 0.01mg/ml fluorescein sodium salt (FNa) prepared using PBS. Sliding loads with a non-stationary contact area were applied across the articular surface by a custom apparatus using a 4.5 mm diameter spherical indenter. A moving contact area was chosen to represent physiological joint motions. Reciprocal sliding was maintained at a rate of 5 mm/s for 2 and 4 hours. Control samples were subject to passive diffusion for 0, 4, and 88 hours. After diffusion tests, samples were snap frozen and 20 µm cross-sectional cuts were taken perpendicular to the sliding direction. Samples were imaged using a Zeiss AxioImager M2 epifluorescent microscope under 5× magnification with a filter for FNa. Intensity profiles were mapped from the articular surface to the subchondral bone. Unloaded control samples demonstrated minimal solute uptake at 4 hours penetrating less than 5% of the total cartilage depth. By 88 hours solute penetration had reached the subchondral bone although there was minimal accumulation within the cartilage matrix indicated by the relatively low intensity profile values. Samples that had been subjected to reciprocal sliding demonstrated accelerated penetration and solute accumulation compared to unloaded samples. After 1 hour of reciprocal sliding, the solute had reached 40% of the cartilage depth, this increased to approximately 80% at 4 hours, with much higher intensities compared to unloaded controls. Sliding motion plays an important role in the uptake of solutes into the cartilage matrix. Maintaining joint motion both post injury and in the arthritic process is a critical component of cartilage nutrition. Samples that had been subject to reciprocal sliding demonstrated accelerated solute penetration and accumulation in the cartilage matrix, exceeding steady state concentrations achieved by passive diffusion

The sternoclavicular joint is vulnerable to the same disease processes as other synovial joints, the most common of which are instability from injury, osteoarthritis, infection and rheumatoid disease. Patients may also present with other conditions, which are unique to the joint, or are manifestations of a systemic disease process. The surgeon should be aware of these possibilities when assessing a patient with a painful, swollen sternoclavicular joint

Osteoarthritis is a global problem and the treatment of early disease is a clear area of unmet clinical need. Treatment strategies include cell therapies utilising chondrocytes e.g. autologous chondrocyte implantation and mesenchymal stem/stromal cells (MSCs) e.g. microfracture. The result of repair is often considered suboptimal as the goal of treatment is a more accurate regeneration of the tissue, hyaline cartilage, which requires a more detailed understanding of relevant biological signalling pathways. In this study, we describe a modulator of regulatory pathways common to both chondrocytes and MSCs. The chondrocytes thought to be cartilage progenitors are reported to reside in the superficial zone of articular cartilage and are considered to have the same developmental origin as MSCs present in the synovium. They are relevant to cartilage homeostasis and, like MSCs, are increasingly identified as candidates for joint repair and regenerative cell therapy. Both chondrocytes and MSCs can be regulated by the Wnt and TGFβ pathways. Dishevelled Binding Antagonist of Beta-Catenin (Dact) family of proteins is an important modulator of Wnt and TGFβ pathways. These pathways are key to MSC and chondrocyte function but, to our knowledge, the role of DACT protein has not been studied in these cells. DACT1 and DACT2 were localised by immunohistochemistry in the developing joints of mouse embryos and in adult human cartilage obtained from knee replacement. RNAi of DACT1 and DACT2 was performed on isolated chondrocytes and MSCs from human bone marrow. Knockdown efficiency and cell morphology was confirmed by qPCR and immunofluorescence. To understand which pathways are affected by DACT1, we performed next-generation sequencing gene expression analysis (RNAseq) on cells where DACT1 had been reduced by RNAi. Top statistically significant (p < 0 .05) 200 up and downregulated genes were analysed with Ingenuity® Pathway Analysis software. We observed DACT1 and DACT2 in chondrocytes throughout the osteoarthritic tissue, including in chondrocytes forming cell clusters. On the non-weight bearing and visually undamaged cartilage, DACT1 and DACT2 was localised to the articular surface. Furthermore, in mouse embryos (E.15.5), we observed DACT2 at the interzones, sites of developing synovial joints, suggesting that DACT2 has a role in cartilage progenitor cells. We subsequently analysed the expression of DACT1 and DACT2 in MSCs and found that both are expressed in synovial and bone marrow-derived MSCs. We then performed an RNAi knockdown experiment. DACT1 knockdown in both chondrocyte and MSCs caused the cells to undergo apoptosis within 24 hours. The RNA-seq study of DACT1 silenced bone marrow-derived MSCs, from 4 different human subjects, showed that loss of DACT1 has an effect on the expression of genes involved in both TGFβ and Wnt pathways and putative link to relevant cell regulatory pathways. In summary, we describe for the first time, the presence and biological relevance of DACT1 and DACT2 in chondrocytes and MSCs. Loss of DACT1 induced cell death in both chondrocytes and MSCs, with RNA-seq analysis revealing a direct impact on transcript levels of genes involved in the Wnt and TFGβ signalling, key regulatory pathways in skeletal development and repair

Joint hemiarthroplasty replaces one side of a synovial joint and is a viable alternative to total joint arthroplasty when one side of the joint remains healthy. Most hemiarthroplasty implants used in current clinical practice are made from stiff materials such as cobalt chrome or ceramic. The substitution of one side of a soft cartilage-on-cartilage articulation with a rigid implant often leads to damage of the opposing articular cartilage due to the resulting reductions in contact area and increases in cartilage stress. The improvement of post-operative hemiarthroplasty articular contact mechanics is of importance in advancing the performance and longevity of hemiarthroplasty. The purpose of the present study was to investigate the effect of hemiarthroplasty surface compliance on early in-vitro cartilage wear and joint contact mechanics. Cartilage wear tests were conducted using a six-station pin-on-plate apparatus. Pins were manufactured to have a hemispherical radius of curvature of 4.7 mm using either Bionate (DSM Biomedical) having varying compliances (80A [E=20MPa], 55D [E=35MPa], 75D [E=222MPa], n=6 for each), or ceramic (E=310GPa, n=5). Cartilage plugs were cored from fresh unfrozen bovine knee joints using a 20 mm hole saw and mounted in lubricant-containing chambers, with alpha calf serum diluted with phosphate buffer solution to a protein concentration of 17 g/L. The pins were loaded to 30N and given a stroke length of 10 mm for a total of 50,000 cycles at 1.2 Hz. Volumetric cartilage wear was assessed by comparing three-dimensional cartilage scans before and during wear testing. A two-way ANOVA was used for statistical analysis. To assess hemiarthroplasty joint contact mechanics, 3D finite element modelling (ABAQUS v6.12) was used to replicate the wear testing conditions. Cartilage was modeled using neo-Hookean hyper-elastic material properties. Contact area and peak contact stress were estimated. The more compliant Bionate 80A and 55D pins produced significantly less volumetric cartilage wear compared with the less compliant Bionate 75D and ceramic pins (p 0.05). In terms of joint contact mechanics, the more compliant materials (Bionate 80A and 55D) had significantly lower maximum contact stress levels compared to the less compliant Bionate 75D and ceramic pins (p < 0 .05). The results of this study show a relationship between hemiarthroplasty implant surface compliance and early in vitro cartilage wear, where the more compliant surfaces produced significantly lower amounts of cartilage wear. The results of the joint contact mechanics analysis showed that the more compliant hemiarthroplasty materials produced lower maximum cartilage contact stresses than the less compliant materials, likely related to the differences in wear observed. More compliant hemiarthroplasty surfaces may have the potential to improve post-operative cartilage contact mechanics by increasing the implant-cartilage contact area while reducing peak contact stress at the implant-cartilage interface, however, such materials must be resistant to surface fatigue and longer-term cartilage wear/damage must be assessed

Objectives. Sustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated in vivo animal model of knee arthrofibrosis. Materials and Methods. A total of 96 rabbits were randomly and equally assigned to four different groups: arthrotomy alone; arthrotomy and collagen scaffold placement; contracture surgery; and contracture surgery and collagen scaffold placement. Animals were killed in equal numbers at 72 hours, two weeks, eight weeks, and 24 weeks. Joint contracture was measured, and cartilage and synovial samples underwent histological analysis. Results. Animals that underwent arthrotomy had equivalent joint contractures regardless of scaffold implantation (-13.9° versus -10.9°, equivalence limit 15°). Animals that underwent surgery to induce contracture did not demonstrate equivalent joint contractures with (41.8°) or without (53.9°) collagen scaffold implantation. Chondral damage occurred in similar rates with (11 of 48) and without (nine of 48) scaffold implantation. No significant difference in synovitis was noted between groups. Absorption of the collagen scaffold occurred within eight weeks in all animals. Conclusion. Our data suggest that intra-articular implantation of a collagen sponge does not induce synovitis or cartilage damage. Implantation in a native joint does not seem to induce contracture. Implantation of the collagen sponge in a rabbit knee model of contracture may decrease the severity of the contracture. Cite this article: J. A. Walker, T. J. Ewald, E. Lewallen, A. Van Wijnen, A. D. Hanssen, B. F. Morrey, M. E. Morrey, M. P. Abdel, J. Sanchez-Sotelo. Intra-articular implantation of collagen scaffold carriers is safe in both native and arthrofibrotic rabbit knee joints. Bone Joint Res 2016;6:162–171. DOI: 10.1302/2046-3758.63.BJR-2016-0193

Inflammation has been associated with early degradative changes in articular cartilage and immune responses are key factor influencing normal tissue regeneration and repair. With synovitis a prominent feature in osteoarthritis (OA) and associated with the progressive degradation of articular cartilage, immune factors need to be factored into efforts to achieve efficient cartilage repair/regeneration. Recent efforts have focused on the use of autologous or allogeneic mesenchymal stem/stromal cells (MSCs) to modulate the inflammatory environment in the injured or osteoarthritic joint. Intraarticular injection of MSCS has modulated cartilage degradation in a variety of pre-clinical OA models. Results from early clinical trials have also shown effects on pain and function-associated outcome measures. Other cell types may also have some capacity for use as a therapy for OA. For example, primary allogeneic chondrocytes also seem to have some immune-privilege in the synovial joint and are immunomodulatory in a rat model. Although MSCs isolated from bone marrow that are induced to undergo chondrogenic differentiation do not retain these properties, MSCs isolated from the synovium or chondroprogenitors generated from cartilage itself may represent the future of cell therapy for OA

Objective. Excessive mechanical stress on synovial joints causes osteoarthritis (OA) and results in the production of prostaglandin E2 (PGE2), a key molecule in arthritis, by synovial fibroblasts. However, the relationship between arthritis-related molecules and mechanical stress is still unclear. The purpose of this study was to examine the synovial fibroblast response to cyclic mechanical stress using an in vitro osteoarthritis model. Method. Human synovial fibroblasts were cultured on collagen scaffolds to produce three-dimensional constructs. A cyclic compressive loading of 40 kPa at 0.5 Hz was applied to the constructs, with or without the administration of a cyclooxygenase-2 (COX-2) selective inhibitor or dexamethasone, and then the concentrations of PGE2, interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), IL-6, IL-8 and COX-2 were measured. Results. The concentrations of PGE2, IL-6 and IL-8 in the loaded samples were significantly higher than those of unloaded samples; however, the concentrations of IL-1β and TNF-α were the same as the unloaded samples. After the administration of a COX-2 selective inhibitor, the increased concentration of PGE2 by cyclic compressive loading was impeded, but the concentrations of IL-6 and IL-8 remained high. With dexamethasone, upregulation of PGE2, IL-6 and IL-8 was suppressed. Conclusion. These results could be useful in revealing the molecular mechanism of mechanical stress in vivo for a better understanding of the pathology and therapy of OA. Cite this article: Bone Joint Res 2014;3:280–8

Paratenonitis describes inflammation of the paratenon and commonly presents as an overuse injury. The paratenon is the connective tissue sheath that surrounds tendons - including tendo Achilles, and serves to minimise friction with the outer layer of the tendon, the epitenon. Whilst this conjunction allows the tendon to glide smoothly on muscular contraction, the presentation of paratenonitis typically follows periods of frequent, repetitive musculoskeletal movements; hence, paratenonitis commonly afflicts the elite and, albeit to a lesser extent, amateur athlete. The extent to which friction at the epitenon-paratenon juncture contributes to this tendinopathy remains unclear, and this study is therefore concerned with the coefficient of friction and the lubrication regime. By using a specially designed and validated apparatus, the in vivo paratenon-epitenon conjunction was approximated using bovine flexor tendon paratenon and a glass disc; this is being an equivalent experimental set-up to that used in other studies exploring soft tissue contacts. Bovine synovial fluid was used to lubricate the conjunction at 37 deg C, and the frictional characteristics were analysed over a range of sliding speeds and loads. The coefficient of friction was found to generally lie between 0.1 – 0.01. This range suggests that a system of mixed lubrication applies - where the synovial fluid is causing partial separation of the two surfaces. However, when the data is plotted in the form of a Stribeck curve, the trend suggests that boundary lubrication prevails - where lubrication is determined by surface-bound proteins. The coefficient of friction at the epitenon-paratenon interface appears to be approximately one order of magnitude greater than that typically reported within the healthy synovial joint. Additionally, the synovial joint is thought to exhibit some fluid film lubrication (i.e. total surface separation), whereas the epitenon-paratenon lubrication regime appears to vary only between the inferior mixed and boundary systems - depending on the specific biomechanical conditions. This data would suggest that the coefficient of friction at the epitenon-paratenon interface is relatively high and thus is potentially significant in the incidence of paratenonitis. Such a hypothesis could be of particular interest to sports-medicine and orthopaedic specialists