Research progress on ROS-responsive hydrogels for the treatment of osteoporosis: a review

Reactive oxygen species (ROS) play a dual role in both physiological and pathological processes, with increased levels being implicated in the pathogenesis of various diseases. ROS-responsive hydrogels, characterized by their hydrophilicity, softness, and superior biocompatibility, have emerged as promising smart materials for targeted therapeutic applications with minimized side effects. Osteoporosis, characterized by decreased bone mass and structural deterioration, is closely associated with oxidative stress and can be classified into two types: primary osteoporosis and secondary osteoporosis. This review provides a comprehensive overview of the principal methods for crosslinking ROS-responsive hydrogels, encompassing physical, chemical, and biological crosslinking approaches, and summarized their delivery strategies as well as modifications designed to enhance targeting selectivity. Additionally, one of their significant biological applications, namely wound healing was discussed. Finally, the therapeutic applications of ROS-responsive hydrogels in both primary and secondary osteoporosis were systematically reviewed. For primary osteoporosis, the discussion was structured according to the pathological timeline of disease progression. And the secondary osteoporosis part was addressed through representative examples-diabetes-related osteoporosis, periodontitis-related osteoporosis, and glucocorticoid-induced osteoporosis-with a focus on their distinct pathogenic mechanisms. By providing a comprehensive overview, this review aims to deepen the understanding of ROS-responsive hydrogels in osteoporosis therapy, while encouraging further research into intelligent and stimuli-responsive biomaterials.