Aims. Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular release. This model allows testing of antifibrotic agents, such as rosiglitazone. Methods. A total of 20 rabbits underwent contracture-forming surgery. Eight weeks later, the animals underwent a surgical capsular release. Ten animals received rosiglitazone (intramuscular initially, then orally). The animals were sacrificed following 16 weeks of free cage mobilisation. The joints were tested biomechanically, and the posterior capsule was assessed histologically and via genetic microarray analysis. Results. There was no significant difference in post-traumatic contracture between the rosiglitazone and control groups (33° (standard deviation (. sd. ) 11) vs 37° (. sd. 14), respectively; p = 0.4). There was no difference in number or percentage of myofibroblasts. Importantly, there were ten genes and 17 pathways that were significantly modulated by rosiglitazone in the posterior capsule. Discussion. Rosiglitazone significantly altered the genetic expression of the posterior capsular tissue in a rabbit model, with ten genes and 17 pathways demonstrating significant modulation. However, there was no significant effect on biomechanical or histological properties. Cite this article: M. P. Abdel. Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis. Bone Joint Res 2016;5:11–17. doi: 10.1302/2046-3758.51.2000593

Introduction and Objective. Joint malleolar fractures have been estimated around 9% of all fractures. They are characterized by different both early and late complications. Among the latter, arthrofibrosis and early secondary arthrosis represent the two most common ones. Moreover, these two complications could be considered related to each other. Their real cause is still under investigation, even if residual post-operative hematoma and acute post-traumatic synovitis appear to be the most accredited. Supporting this hypothesis, joint debridement and the evacuation of the post-operative hematoma could represent a possible solution. The aim of this prospective study is to evaluate the role of arthroscopic lavage and debridement during internal fixation in order to prevent late joint complications. Materials and Methods. Sixty consecutive patients who reported dislocated articular ankle fractures with surgical indication of open reduction and internal fixation (ORIF) have been included in this study. 27 patients underwent ORIF surgery associated with arthroscopic washout and debridement, while 33 patients, representing the control group, underwent just internal reduction and osteosynthesis. Patients with pure dislocations, non-articular fractures, polytrauma, previous local trauma, metabolic and connective pathologies were excluded. Follow-up was performed at 40 days (T1), 3 (T2) and 6 months (T3) after trauma for all patients. If necessary, some have been re-evaluated 12 months after the trauma. Efficacy of the treatment was evaluated through the VAS scale, Maryland scale, search for local complications such as dehiscence or infections, and finally radiographic evaluation. T-Student was estimated in order to individuate statistical significance. Results. VAS scale showed higher values for the case group than the control group with mean values of 2.7 and 4.2 at T1 and 2.1 and 3.8 at T2, respectively. At 6 months follow-up, the VAS values resulted similar with 2.6 for the case group and 2.8 for the control group. The same projections were found for the Maryland scale, with values of 61.5 and 40.7 at T1, 80.8 and 68.0 at T2 and 87.8 and 85.0 with no significant differences at T3 respectively. No significant differences were detected for complications or radiographic evaluation. Conclusions. Our study has shown significance differences in terms of pain and time for recovery only in the very short term follow up. Although our study, due to the specific limits, cannot be considered diriment, on the basis of the data, we could hypothesize that the aforementioned hypothesis may remain valid for the non-acute hematoma or that the cause of the arthrofibrosis should be sought somewhere else. However, evidence is low, and further research is needed

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

Summary. Based upon genetic analysis, decorin is an exciting pharmacologic agent of potential anti-fibrogenic effect on arthrofibrosis in our animal model. Introduction. While the pathophysiology of arthrofibrosis is not fully understood, some anti-fibrotic molecules such as decorin could potentially be used for the prevention or treatment of joint stiffness. The goal of this study was to determine whether intra-articular administration of decorin influences the expression of genes involved in the fibrotic cascade ultimately leading to less contracture in an animal model. Material and Methods. Eighteen rabbits had their right knees operated on to form contractures. The left knees served as controls. The 6 right limbs in the experimental group (Group 1) received four 500 ug/ml intra-articular injections of decorin over 8 days starting at 8 week, for a total of 2 mg. The 6 right limbs in the first control group (Group 2) received four intra-articular injections of bovine serum albumin (BSA) over 8 days starting at 8 weeks as well. The 6 six right limbs in the second control group (Group 3) received no injections. The contracted limbs of rabbits in Group 1 were biomechanically and genetically compared to the contracted limbs of rabbits in Groups 2 and 3 with the use of a calibrated joint measuring device and custom microarray, respectively. Results. There was no statistical difference in the flexion contracture angles between those right limbs that received intra-articular decorin versus those that received intra-articular BSA (66° vs. 69°; p = 0.41). Likewise, there was no statistical difference between those right limbs that received intra-articular decorin as opposed to those who had no injection (66° vs. 72°; p = 0.27). The lack of significance remained when the control left limbs were taken into account (p > 0.40). When compared to bovine serum albumin (BSA), decorin led to a statistically significant increase in the mRNA expression of 5 genes: substance P, neuropeptide γ, and neurokinin A, cyclin E2, and MMP-9 (p < 0.001). In addition, there was a statistically significant decrease in fibroblast growth factor receptor-2 (FGFR-2), rho-associated coiled-coil containing protein kinase-1 (ROCK-1), and vascular cell adhesion molecule-1 (VCAM-1) genes when intra-articular decorin was compared to no injection (p < 0.001). Conclusions. In this model, when administered intra-articularly at 8 weeks, 2 mg of decorin had no significant effect on joint contractures. However, our genetic analysis revealed a significant alteration in the expression of several fibrotic genes. Further studies investigating the route of administration, dosing, frequency, and timing are required before definitive conclusions may be drawn on the effects of decorin on joint contractures

Osteochondral lesions (OCLs) of the talus are a challenging and increasingly recognized problem in chronic ankle pain. Many novel techniques exist to attempt to treat this challenging entity. Difficulties associated with treating OCLs include lesion location, size, chronicity and problems associated with potential graft harvest sites. Matrix associated stem cell transplantation (MAST) is one such treatment described for larger lesions >15mm. 2. or failed alternative therapies. This cohort study describes a 5 year review of the outcomes of talar lesions treated with MAST. A review of all patients treated with MAST by a single surgeon was conducted. Pre-operative radiographs, MRIs and FAOS outcome questionnaire scores were conducted. Intraoperative classification was conducted to correlate with imaging. Post-operative outcomes included FAOS scores, return to sport, revision surgery/failure of treatment and progression to arthritis/fusion surgery. 32 patients were identified in this cohort. There were 10 females, 22 males, with an average age of 35. 01. 73% had returned and continued playing active sport. 23 patients underwent MAST in the setting of a failed previous operative attempt, with just 9 having MAST as a first option. 9 patients out of 32 had a further procedure. Two patients had a further treatment directed at their OCL. Two patients had a fusion, 2 had a cheilectomy at > 4 years for impingement, one had a debridement of their anterolateral gutter, one had debridement for arthrofibrosis, one patient had a re alignment calcaneal osteotomy with debridement of their posterior tibial tendon. MAST has demonstrated positive results in lesions which prove challenging to treat, even in a “failed microfracture” cohort

We attempted to repair full-thickness defects in the articular cartilage of the trochlear groove of the femur in 30 rabbit knee joints using allogenic cultured chondrocytes embedded in a collagen gel. The repaired tissues were examined at 2, 4, 8, 12 and 24 weeks after operation using histological and histochemical methods. The articular defect filling index measurement was derived from safranin-O stained sections. Apoptotic cellular fractions were derived from analysis of apoptosis in situ using TUNEL staining, and was confirmed using caspase-3 staining along with quantification of the total cellularity. The mean articular defect filling index decreased with time. After 24 weeks it was 0.7 (sd 0.10), which was significantly lower than the measurements obtained earlier (p < 0.01). The highest mean percentage of apoptotic cells were observed at 12 weeks, although the total cellularity decreased with time. Because apoptotic cell death may play a role in delamination after chondrocyte transplantation, anti-apoptotic gene therapy may protect transplanted chondrocytes from apoptosis.

Ovine articular chondrocytes were isolated from cartilage biopsy and culture expanded in vitro. Approximately 30 million cells per ml of cultured chondrocytes were incorporated with autologous plasma-derived fibrin to form a three-dimensional construct. Full-thickness punch hole defects were created in the lateral and medial femoral condyles. The defects were implanted with either an autologous ‘chondrocyte-fibrin’ construct (ACFC), autologous chondrocytes (ACI) or fibrin blanks (AF) as controls. Animals were killed after 12 weeks. The gross appearance of the treated defects was inspected and photographed. The repaired tissues were studied histologically and by scanning electron microscopy analysis.

All defects were assessed using the International Cartilage Repair Society (ICRS) classification. Those treated with ACFC, ACI and AF exhibited median scores which correspond to a nearly-normal appearance. On the basis of the modified O’Driscoll histological scoring scale, ACFC implantation significantly enhanced cartilage repair compared to ACI and AF. Using scanning electron microscopy, ACFC and ACI showed characteristic organisation of chondrocytes and matrices, which were relatively similar to the surrounding adjacent cartilage.

Implantation of ACFC resulted in superior hyaline-like cartilage regeneration when compared with ACI. If this result is applicable to humans, a better outcome would be obtained than by using conventional ACI.