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Specifically, the pro-angiogenic, neurotrophic, and anti-inflammatory effects of EVs were reinforced through three-dimensional culture and dexamethasone (Dxm) encapsulation. Then, the prepared Dxm-loaded 3EVs (3EVs-Dxm) were membrane modified with ortho-dihydroxy groups (-2OH) and formed an EV-integrated hydrogel (3EVs-Dxm-Gel) via the cross-link with phenylboronic acid\u2013modified hyaluronic acid and tannic acid. The phenylboronic acid ester in 3EVs-Dxm-Gel enabled effective immobilization and reactive oxygen species\u2013responsive release of EVs. Topical injection of 3EVs-Dxm-Gel in SCI rats notably mitigated injury severity and promoted functional recovery, which may offer opportunities for EV-based therapeutics in central nervous system injury.<\/jats:p>","DOI":"10.1126\/sciadv.ads3398","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T16:33:04Z","timestamp":1743611584000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":98,"title":["An engineering-reinforced extracellular vesicle\u2013integrated hydrogel with an ROS-responsive release pattern mitigates spinal cord injury"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4299-9484","authenticated-orcid":true,"given":"Jian","family":"Cao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, 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