Engineered nasal cartilage for the repair of osteoarthritic knee cartilage defects

Background \u0026 Aim Osteoarthritis (OA) is the most prevalent joint disorder causing pain and disability predominantly in the ageing population but also in young individuals. Current treatments are limited to alleviate symptoms, e.g. with anti-inflammatory drugs, until at the end stage of the disease the degenerated joint is replaced by a prosthetic implant. In this study we hypothesize that degenerative cartilage defects can be treated using Nasal chondrocyte-based Tissue Engineered Cartilage (N-TEC), as previously applied for the repair of focal articular cartilage lesions. In particular, we tested (i) the response of N-TECs to inflammatory factors, (ii) their capacity to modulate the inflammatory profile of OA joint cells in vitro as well as (iii) their survival in - and integration with OA tissues in vivo. Based on these results we then (iv) assessed the performance of N-TEC upon implantation in OA knee cartilage lesions of human patients. Methods, Results \u0026 Conclusion When N-TEC was exposed in vitro to inflammatory stimuli, as those found in OA joints (IL-1β/TNFα/IL-6 cytokines or factors secreted by OA synoviocytes) we demonstrate that it maintained its cartilaginous properties (i). Moreover, the secretome of N-TEC positively influenced the inflammatory profile of cells from OA joints, i.a. by reducing the expression of IL-6 and TNFα (ii). In vivo in an ectopic mouse model reproducing a human osteochondral OA tissue environment as well as in chronified articular cartilage defects in sheep, we further demonstrated cell survival and engraftment of N-TEC with the surrounding OA tissues (iii). Finally, we tested clinically the implantation of autologous N-TEC in two patients with advanced OA (Kellgren and Lawrence grade 3 and 4), who were otherwise considered for unicondylar knee arthroplasty. Patients reported reduced pain as well as improved joint function and life quality 14 months after surgery. In addition, a radiologically observed increase in joint space, indicating safety and feasibility of the treatment (iv). Together, our findings indicate that N-TEC can directly contribute to cartilage repair in OA joints. A phase II clinical trial is now required to assess efficacy in a larger cohort of OA patients.