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The hostile post\u2010injury microenvironment, marked by excessive oxidative stress, inflammatory responses, and progressive neuronal degeneration, greatly limits neural repair. In this study, we developed a multifunctional reactive oxygen species (ROS)\u2010scavenging hydrogel composed of N\u2010acryloylglycylamide (NAGA), xanthan gum (XG), carbomer 940 (CBP940), and tannic acid (TA) (termed NXCT) to locally deliver glial cell line\u2010derived neurotrophic factor (GDNF)\u2010enriched small extracellular vesicles (sEVs). GDNF, as a key neurotrophic protein, was incorporated into engineered sEVs to enhance their neuroregenerative activity. The resulting GDNF\u2010sEVs@NXCT hydrogel exhibited favorable antioxidant and anti\u2010inflammatory properties in vitro and effectively supported neuronal survival and axonal regeneration. After in situ implantation into the injured spinal cord, GDNF\u2010sEVs@NXCT reduced ROS accumulation, alleviated inflammatory responses, promoted neural and myelin regeneration, and enhanced motor functional recovery in SCI rats. RNA\u2010sequencing further uncovered that these therapeutic effects of GDNF\u2010sEVs@NXCT were associated with PI3K\/AKT pathway activation. Overall, these results demonstrate that the GDNF\u2010sEVs@NXCT hydrogel provides a bioactive macromolecule\u2010based therapeutic strategy for SCI repair via microenvironment modulation and neuroregeneration, highlighting its translational potential for spinal cord repair.<\/jats:p>","DOI":"10.1002\/adhm.71806","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:28:26Z","timestamp":1791268106000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GDNF\u2010Enriched Small Extracellular Vesicle\u2010Loaded ROS\u2010Scavenging Hydrogel Promotes Neural Regeneration After Spinal Cord Injury"],"prefix":"10.1002","author":[{"given":"Xingyu","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Orthopedics Affiliated People's Hospital of Jiangsu University  Zhenjiang P.R. 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