Dual-functional ROS-responsive hydrogel alleviates temporomandibular joint osteoarthritis by enhancing cartilage repair and mitigating inflammation.

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by variable degrees of inflammatory cartilage degeneration and subchondral bone erosion. Current clinical treatments mainly focus on symptomatic relief, such as pain management, and no disease-modifying osteoarthritis (OA) drugs (DMOADs) have been approved for widespread clinical use by regulatory bodies. Although fibroblast growth factor (FGF18) has shown great potential to be DMOADs in clinical trials for OA treatment by stimulating cartilage regeneration, its efficacy of inducing anabolic responses in articular cartilage is significantly limited by inflammatory conditions. In this study, we delivered FGF18 using an innovative hydrogel that underwent responsive degradation in the reactive oxygen species (ROS)-enriched TMJOA sites, continuously delivering the cartilage-repairing FGF18 and consuming ROS, further counteracting the limitation of inflammatory factors on cartilage repair ability of FGF18, thereby hindering the progression of TMJOA. This is the first attempt to hinder TMJOA progression with FGF18, and has demonstrated the dual function of hydrogel in reducing inflammation levels and promoting cartilage repair in TMJOA environment. This discovery addresses the limitations of short retention time of FGF18 in clinical applications, and also provides a new strategy for improving articular cartilage repair by overcoming the inflammatory environment.