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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\u2014diabetes-related osteoporosis, periodontitis-related osteoporosis, and glucocorticoid-induced osteoporosis\u2014with 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.<\/jats:p>","DOI":"10.1088\/1748-605x\/ae5566","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T22:51:49Z","timestamp":1774047109000},"page":"022007","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Research progress on ROS-responsive hydrogels for the treatment of osteoporosis: a review"],"prefix":"10.1088","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7005-047X","authenticated-orcid":true,"given":"Yuhan","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihao","family":"Lan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lanyue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1657-8723","authenticated-orcid":true,"given":"Duoling","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8384-0977","authenticated-orcid":true,"given":"Chao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"266","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"bmmae5566bib1","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.jare.2024.05.024","type":"journal-article","article-title":"A comprehensive review and advanced biomolecule-based therapies for osteoporosis","volume":"71","author":"Ali","year":"2025","journal-title":"J. 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