Piramal (Canada)

BackgroundIn this study we evaluated a novel approach to guide the bone marrow-driven articular cartilage repair response in skeletally aged rabbits. We hypothesized that dispersed chitosan particles implanted close to the bone marrow degrade in situ in a molecular mass-dependent manner, and attract more stromal cells to the site in aged rabbits compared to the blood clot in untreated controls.MethodsThree microdrill hole defects, 1.4 mm diameter and 2 mm deep, were created in both knee trochlea of 30 month-old New Zealand White rabbits. Each of 3 isotonic chitosan solutions (150, 40, 10 kDa, 80% degree of deaceylation, with fluorescent chitosan tracer) was mixed with autologous rabbit whole blood, clotted with Tissue Factor to form cylindrical implants, and press-fit in drill holes in the left knee while contralateral holes received Tissue Factor or no treatment. At day 1 or day 21 post-operative, defects were analyzed by micro-computed tomography, histomorphometry and stereology for bone and soft tissue repair.ResultsAll 3 implants filled the top of defects at day 1 and were partly degraded in situ at 21 days post-operative. All implants attracted neutrophils, osteoclasts and abundant bone marrow-derived stromal cells, stimulated bone resorption followed by new woven bone repair (bone remodeling) and promoted repair tissue-bone integration. 150 kDa chitosan implant was less degraded, and elicited more apoptotic neutrophils and bone resorption than 10 kDa chitosan implant. Drilled controls elicited a poorly integrated fibrous or fibrocartilaginous tissue.ConclusionsPre-solidified implants elicit stromal cells and vigorous bone plate remodeling through a phase involving neutrophil chemotaxis. Pre-solidified chitosan implants are tunable by molecular mass, and could be beneficial for augmented marrow stimulation therapy if the recruited stromal cells can progress to bone and cartilage repair.

Background Microfracture and drilling are bone marrow–stimulation techniques that initiate cartilage repair by providing access to cell populations in subchondral bone marrow. This study examined the effect of hole depth and of microfracture versus drilling on subchondral bone repair and cartilage repair in full-thickness chondral defects. Hypotheses Repaired subchondral bone does not reconstitute its native structure and exhibits atypical morphologic features. Drilling deeper induces greater bone remodeling and is related to improved cartilage repair. Study Design Controlled laboratory study. Methods Trochlear cartilage defects debrided of the calcified layer were prepared bilaterally in 16 skeletally mature rabbits. Drill holes were made to a depth of 2 mm or 6 mm and microfracture holes to 2 mm. Animals were sacrificed 3 months postoperatively, and joints were scanned by micro–computed tomography before histoprocessing. Bone repair was assessed with a novel scoring system and by 3-dimentional micro–computed tomography and compared with intact controls. Correlation of subchon-dral bone features to cartilage repair outcome was performed. Results Although surgical holes were partly repaired with mineralized tissue, atypical features such as residual holes, cysts, and bony overgrowth were frequently observed. For all treatment groups, repair led to an average bone volume density similar to that of the controls but the repair bone was more porous and branched as shown by significantly higher bone surface area density and connectivity density. Deeper versus shallower drilling induced a larger region of repairing and remodeling subchondral bone that positively correlated with improved cartilage repair. Conclusion Incomplete reconstitution of normal bone structure and continued remodeling occurred in chondral defects 3 months after bone marrow stimulation. Deep drilling induced a larger volume of repairing and remodeling bone, which appeared beneficial for chondral repair. Clinical Relevance Bone marrow stimulation does not reconstitute normal bone structure. Strategies that increase subchondral bone involvement in marrow stimulation could further benefit cartilage repair.