Photo-responsive biomimetic catalytic hydrogel–nanocatalytic-mediated osteoclast fate regulation

• Demonstrates excellent light-responsive properties and can effectively control the release of ROS. • Inhibition of osteoclast differentiation. • Non-invasive and improves the efficiency of RA treatment. • ROS generated by photoexcitation of curcumin triggers the conversion of cuprous oxide to copper oxide. The main reasons why the current treatment methods for rheumatoid arthritis are not efficient in treating RA at present are insufficient drug control and the inability of surgery to repair the damage. In this study, a multifunctional hydrogel was constructed by cross-linking β-cyclodextrin with sodium alginate to synergistically utilize the photodynamic effect and arthritis therapeutic activity of curcumin. Based on the cuprous oxide/calcium peroxide complex system, the ROS produced by photoexcitation of curcumin can trigger the conversion of cuprous oxide to copper oxide, while the continuous oxygen supply of calcium peroxide enhances the efficacy of PDT. The combined effect jointly inhibits the differentiation of osteoclasts. This system forms a self-regulating collaborative treatment system through the linkage mechanism of “ROS generation − oxygen supply − bone repair”. This catalytic composite hydrogel exhibits excellent photoresponse characteristics. Compared with the second-generation traditional photosensitizers, it significantly reduces the subsequent generation of ROS, confirming its precisely controllable ROS generation ability. Moreover, by synergistic regulating the GPX4-mediated ferroptosis pathway, it promotes ferroptosis in osteoclasts in vitro. In the rat model of collagen-induced arthritis, the precise controlled-release characteristics of this system effectively inhibited osteoclast differentiation, significantly improving the pathological progression of the joints.