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As a master regulator of antioxidant and anti\u2010inflammatory defenses, nuclear factor erythroid 2\u2010related factor 2 (Nrf2) represents a promising therapeutic target. However, current strategies for Nrf2 activation remain limited in achieving durable synovial gene expression and pathology\u2010adaptive release. Here, we developed an injectable inflammation\u2010responsive nanocolloidal hydrogel enabling sustained and on\u2010demand Nrf2 activation within OA joints. The hydrogel was fabricated by crosslinking polyvinyl alcohol (PVA) with phenylboronic acid (PBA)\u2010functionalized nanoparticles encapsulating Nrf2 plasmids. Dynamic boronate ester linkages between PBA and PVA enabled rapid in situ gelation after intra\u2010articular injection. In the ROS\u2010enriched inflammatory microenvironment of OA, cleavage of boronate ester bonds triggered the release of Nrf2 plasmid\u2010loaded nanoparticles. The released nanoparticles were efficiently internalized by fibroblast\u2010like synoviocytes (FLSs) and promoted Nrf2 expression, thereby suppressing oxidative stress and inflammatory responses. In ACLT\u2010induced OA mice, the hydrogel markedly alleviated synovial inflammation, preserved cartilage matrix, and reduced the OARSI score by approximately 70%. These findings highlight its potential as a promising strategy for inflammation\u2010adaptive gene regulation in OA therapy.<\/jats:p>","DOI":"10.1002\/adhm.71557","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T04:36:02Z","timestamp":1786077362000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammation\u2010Responsive Nanocolloidal Hydrogel Enables On\u2010Demand Gene Activation for Osteoarthritis Therapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Yuexin","family":"Zhao","sequence":"first","affiliation":[{"name":"Taishan People's Hospital Postdoctoral Innovation Practice Base of Southern Medical University  Taishan China"},{"name":"Division of Orthopaedics and Traumatology Department of Orthopaedics Nanfang Hospital Southern Medical University  Guangzhou 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