Cell-based bioactive materials for osteoarthritis therapy: a comprehensive review

Osteoarthritis (OA) is multifactorial degenerative joint diseases with high incidence and heavy burden on human health and the world economy. Conventional approaches to combat OA have certain therapeutic efficacy. However, these treatments can inadvertently harm healthy tissues and lead to various complication. Biomaterials have emerged as a promising alternative due to their enhanced effectiveness, precise targeting, and spatiotemporal controllability. Despite these benefits, synthetic biomaterials - particularly inorganic nanomaterials used as drug delivery vehicles or direct therapeutic agents (e.g., ROS-scavenging nanozymes, lubricants, and photothermal platforms) - still face challenges such as rapid synovial clearance, limited cartilage penetration, and potential biocompatibility concerns, which have impeded their broader clinical application in OA treatment. To address these limitations, cell-based biomaterials leverage the intrinsic properties of cells-such as chemotaxis, homing ability, and biocompatibility-to design advanced therapeutic systems tailored for joint microenvironments. In this review, we first provide an analysis of OA abnormalities, including biophysical, cellular, and biochemical aspects. Then, we describe the design principles of cell-based biomaterials based on these abnormalities. Afterwards, we summarize various varieties of cell-based biomaterials and the recent advances of their applications in OA treatment. Finally, we explore the current challenges and prospects of cell-based biomaterials.