The challenge of articular cartilage repair : studies on cartilage repair in animal models and in cell culture

Articular cartilage is highly specialized tissue that covers the ends of bones in joints. The intrinsic repair capacity of cartilage is poor due to the avascular nature of the tissue. The prevalence of cartilage defects is expected to increase, and if untreated, they may lead to premature osteoarthritis, the world’s leading joint disease. Surgical cartilage repair techniques aim at improving joint function and ceasing the degeneration progress. Implantable biomaterial scaffolds have been developed to create a supporting structure for regenerating cartilage tissue. Despite promising short term results, a material that is able to support the formation of durable hyaline cartilage is yet to be developed. The feasibility of a novel composite material rhCo-PLA that combines recombinant human type II collagen and poly(L/D)lactide felt was tested in a porcine model together with autologous chondrocytes. The scaffold resulted in repair tissue similar to a clinically used commercial collagen membrane. Subchondral bone lesions beneath the repair site developed in all study groups but the novel scaffold resulted in fewer bone defects than the commercial control. Damaged subchondral bone might require filler material in order to restore the height of the cartilage surface and joint congruence. The repair of deep osteochondral defects with porous poly-lactic-co-glycolic acid (PLGA) scaffolds and scaffolds combining PLGA with bioactive glass (BG) fibers (PLGA-BGf) was studied in a lapine model. PLGA resulted in bone volume fraction similar to that of spontaneous healing. PLGA-BGf worsened the repair and the defects were filled with loose connective tissue instead of bone. Commercial controls, beta-tricalcium phosphate and BG granules, resulted in extensive bone formation. Animal models are used in the development of new treatment options. In order to improve the effectiveness and ethical use of the equine model in cartilage repair, spontaneous repair capacity of equine carpal cartilage was evaluated to find the critical lesion size beyond which spontaneous repair does not occur. We found out that 2 mm is the critical lesion size for chondral lesions and 4 mm for osteochondral defects. Autologous chondrocytes have been used in cartilage repair for more than 20 years but their amount is limited and they require two separate surgeries. Bone marrow-derived human mesenchymal stem cells can be used as an alternative cell source. Predifferentiation of these cells in rhCo-PLA scaffolds manufactured either with type II or type III collagen was evaluated in vitro. Chondrogenic differentiation resulted in chondrocyte hypertrophy at an early phase of cell culture. The different collagen types in rhCo-PLA scaffolds did not affect the outcomes. All animal models used in this study demonstrated that subchondral bone defects are associated with cartilage defects and repair procedures. This emphasizes the fact that the synovial joint is a functional unit comprised of several tissues and the challenge of cartilage repair is further complicated by comorbidities in the adjacent tissues.