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Current therapies partially promote axonal regeneration but rarely achieve meaningful visual recovery, limited mainly by unstable myelin reconstruction and inadequate injury microenvironment modulation. Here, we developed a photo\u2010crosslinkable bilayer hydrogel system (GO\/GI@MPDA\u2010Cle). Its outer layer (GM\u2010Odex) provides strong wet tissue adhesion for optic nerve sheath sealing, while the inner layer (GM\u2010imid) enables sustained local release of drug\u2010loaded nanoparticles (MPDA\u2010Cle) for microenvironment modulation. In Vitro, the system exhibited excellent antioxidant and anti\u2010inflammatory properties and polarized microglia toward an anti\u2011inflammatory phenotype. In a rat partial optic nerve injury model, the hydrogel protected retinal ganglion cells through local immunomodulation and was associated with improved oligodendrocyte\u2010associated maturation and remyelination\u2010associated repair, accompanied by partial improvement in optic nerve conduction\u2010related function. Transcriptomic analysis further revealed that the treatment downregulated pathways related to inflammation, oxidative stress, and neuronal apoptosis, while upregulating genes involved in neuronal regeneration, axonal growth, and myelination. By integrating physical sealing, immunomodulation, and myelin repair, this study proposes a promising multifunctional strategy for optic nerve injury treatment.<\/jats:p>","DOI":"10.1002\/advs.78031","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:00:31Z","timestamp":1790532031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Situ Photo\u2011Crosslinked Functional Bilayer Hydrogel Modulates Local Microenvironment and Remyelination After Optic Nerve Injury"],"prefix":"10.1002","author":[{"given":"Tonghe","family":"Pan","sequence":"first","affiliation":[{"name":"Eye Research Center, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Eye Hospital Wenzhou Medical University  Hangzhou Zhejiang China"},{"name":"Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health)  Wenzhou Zhejiang China"},{"name":"State Key Laboratory of Eye Health, 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