MXenes nanosheets with high conductivity, hydrophilicity, and excellent reactive oxygen species (ROS) scavenging ability have shown promise in treating various degenerative diseases correlated with abnormal ROS accumulation. Herein, the therapeutic potential of Ti₃C₂T_x nanosheets, which is the most widely investigated MXene material, in delaying osteoarthritis (OA) progression is demonstrated. In vitro experiments indicate the strong ROS scavenging capacity of Ti₃C₂T_x nanosheets and their acceptable biocompatibility. Ti₃C₂T_x nanosheets effectively protect chondrocytes from cell death induced by oxidative stress. In addition, Ti₃C₂T_x nanosheets demonstrate a prominent anti-inflammatory effect and the ability to restore homeostasis between anabolic activities and catabolic activities in chondrocytes. Furthermore, RNA sequencing reveals the potential mechanism underlying the Ti₃C₂T_x nanosheet-mediated therapeutic effect. Finally, the in vivo curative effect of Ti₃C₂T_x nanosheets is verified using a rat OA model. Histological staining and immunohistochemical analyses indicate that Ti₃C₂T_x nanosheets effectively ameliorate OA progression. Conclusively, the in vitro and in vivo experiments suggest that Ti₃C₂T_x nanosheets could be a promising and effective option for OA treatment.

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