Cell-based and tissue engineering therapies for cartilage repair and osteoarthritis.

OBJECTIVE: The repair of damaged articular cartilage remains a significant challenge, despite extensive research conducted since the 1970s. This is primarily due to the avascular nature and complex zonal architecture of cartilage and its intricate biomechanics. At present, no pharmacological treatments effectively halt the progression of cartilage breakdown in osteoarthritis. Cell-based and tissue engineering approaches offer innovative solutions for possible life-long cartilage repair. Here, we provide a comprehensive narrative review of the diverse methods for cartilage repair that have been developed and investigated over the years, emphasizing both the successes achieved and the limitations encountered in these approaches.

DESIGN: Relevant publications from 1970 to 2026 were identified using PubMed searches. Given the vast quantity of literature, we focused on cell-based and tissue engineering interventions that were evaluated in vivo. Additionally, clinical trials were reviewed using data from clinicaltrials.gov.

RESULTS: Autologous chondrocyte implantation has been a pioneering technique for the repair of articular cartilage defects. Numerous strategies have since been investigated, including the use of various cells, sophisticated scaffolds, substrates, bioactive molecules, and different combinations thereof. Cell sources utilized include cultured chondrocytes, mesenchymal stromal cells, and induced pluripotent stem cells. Scaffolds and substrates are increasingly advanced, with gradient designs to better mimic natural tissue. Choosing optimal techniques and cell sources remains challenging and context-dependent. Advances in the understanding of developmental and regenerative biology are guiding more informed approaches to cartilage tissue engineering. Insights into joint-resident stem and progenitor cells present new opportunities to activate intrinsic repair processes.

CONCLUSIONS: Regenerative interventions for cartilage repair have the potential to deliver substantial long-term benefits to patients. A wide array of innovative approaches have been explored in recent years. The challenge lies in effectively translating these advances into clinical applications. A one-fits-all solution is unrealistic, and identifying patients who are likely to respond to a specific treatment will enhance success. The repair of joint surface defects in an osteoarthritic joint may require more complex strategies.