Stem cell-based cartilage regeneration: Biological strategies, engineering innovations, and clinical translation.

Abstract

Articular cartilage damage caused by trauma or degenerative diseases such as osteoarthritis remains a major therapeutic challenge due to the tissue's limited regenerative capacity. Traditional surgical interventions-including microfracture, autologous chondrocyte implantation, and osteochondral grafting-often result in the formation of biomechanically inferior fibrocartilage and fail to restore long-term joint function. In contrast, stem cell-based strategies have emerged as a promising approach for regenerating hyaline-like cartilage by combining the biological potential of mesenchymal stem cells and induced pluripotent stem cells with advances in tissue engineering. This review synthesizes the current understanding of cartilage structure and repair limitations, evaluates the regenerative potential of various stem cell sources, and highlights engineering innovations such as bioactive scaffolds, controlled growth factor delivery, and three-dimensional bioprinting. We also examine key preclinical studies and early-phase clinical trials demonstrating the safety and efficacy of stem cell-based therapies. Finally, we explore future directions, including gene editing, exosome-based therapeutics, and personalized regenerative strategies, that may address remaining translational barriers. Collectively, stem cell-centered approaches offer a transformative avenue toward durable, functional cartilage repair and hold strong potential for clinical application.