Implantation and Analysis of a Biphasic Bioinspired Osteochondral Chitosan Construct in a Large Animal Model

Osteochondral defects are severe degenerative lesions of the joint that involve the articular cartilage, the cartilage-bone interface, and the underlying subchondral bone. Surgical approaches that have been developed (joint debridement, microfracture, autologous chondrocytes and autologous/allograft cartilage implantation, and whole joint replacement) remain, however, more palliative than curative. Therefore, novel strategies are required, including promising options offered by osteochondral tissue engineering approaches. In this study, a novel chitosan-based scaffold with biomimetic and biodegradable properties was implanted for 16 weeks in a sheep osteochondral defect model in order to evaluate its physical stability, biocompatibility, and regenerative potential. Alongside the chitosan construct, a commercial scaffold made of collagen and ß-TCP was implanted as a positive control, while defects left empty were used as negative control. Postoperative recovery and tissue response were evaluated at different levels including activity monitoring, gross tissue evaluation at sacrifice, imaging, and histological analysis. Despite a transient reaction observed in the first 4 weeks after implantation, the chitosan-based scaffold was well-tolerated, with no clear signs of local or systemic reaction in the long term. The chitosan scaffold was able to support the growth of mature bone tissue with a lamellar conformation at similar levels to the predicate control. It also promoted the formation of a new cartilage layer, although not at a fully mature stage. These proof-of-concept results suggest that the novel chitosan scaffold tested constitutes a possible option for osteochondral regeneration, which should be further analyzed in complementary models to provide information on its long-term performance.