CONTROLLING THE CELLULAR FATE AND ENHANCING SCAFFOLD DESIGN FOR CARTILAGE AND MENISCUS THERAPIES: TOWARDS CLINICAL TRANSLATION

Osteoarthritis (OA) is one of the most prevalent conditions in the world with approximately 600 million individuals, with cases expected to rise with people undertaking more rigorous and high-risk sporting activities, leading to trauma that can trigger the onset of the disease. Though OA is considered a whole joint disease, therapies have primarily focussed on regenerating articular cartilage. However, its pathogenesis can also arise as a secondary complication from meniscus tears, which alters joint biomechanics and increases exposure of the underlying articular cartilage. Thus, preservation of the surrounding tissues and treating articular cartilage are vital for early OA prevention. Regenerative medicine has yielded a variety of the cell or biomaterial-based strategies for the treatment of articular cartilage and meniscus, although clinical trials have shown mixed results. This is related to an understanding that different types of cartilage or meniscal lesions require a specific remedy, emphasising the need for a personalised medicine-based approach. In articular cartilage repair, cell-based therapies such as autologous chondrocyte implantation (ACI) often results in fibrocartilage formation, thereby necessitating the requirement for additional interventions. In the case of meniscus tears, collagen or PCU scaffolds can replace damaged tissue but long-term studies show that the scaffolds gradually degrade with time and do not provide superior chondroprotection compared to meniscectomy. Controlling the cellular fate in cell-based therapies and functionalising scaffolds with specific motifs have the potential to enhance current regenerative strategies for articular cartilage and meniscus, thereby improving long-term performance and clinical outcomes. This presentation will provide an overview of our work on how environmental stimuli influence chondrocyte and meniscal cell phenotypes and how scaffold functionalisation can potentially enhance its performance in a defect model for meniscus tears. Additionally, the talk will also highlight the advancements in cartilage and meniscus regeneration over past twenty years in Europe and discuss future directions for achieving more effective translation from the bench to the clinic.