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While stem cell\u2010derived extracellular vesicles (EVs) show potential for treating stroke, the results remain unsatisfactory due to the lack of approaches for retaining and controlling EVs released into the brain. Herein, a glucose\/reactive oxygen species dual\u2010responsive hydrogel showing excellent injectability, biocompatibility, and self\u2010healing capability is introduced as an EVs\u2010loading vehicle and an intelligent EVs sustained releasing system in the brain. These EVs\u2010hydrogels are developed via crosslinking of phenylboronic acid\u2010modified hyaluronic acid and Poly vinyl alcohol, and fusion with neural stem cell\u2010derived EVs. The results show EVs are stably incorporated into the hydrogels and can be controllably released in response to the brain microenvironment after stroke in type 2 diabetic mice. The EVs\u2010hydrogels exert an excellent angiogenic effect, increasing the migration and tube formation of human umbilical vein endothelial cells. In addition, injection of EVs\u2010hydrogels into the ischemic mouse brain enhances EVs retention and facilitates sustained release, promotes angiogenesis, and improves neurobehavioral recovery. These results suggest such a microenvironment responsive and sustained release EVs\u2010hydrogel system offers a safe, and efficient therapy for diabetic stroke.<\/jats:p>","DOI":"10.1002\/adhm.202201150","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T16:49:41Z","timestamp":1662569381000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Brain Microenvironment Responsive and Pro\u2010Angiogenic Extracellular Vesicle\u2010Hydrogel for Promoting Neurobehavioral Recovery in Type 2 Diabetic Mice After Stroke"],"prefix":"10.1002","volume":"11","author":[{"given":"Yixu","family":"Jiang","sequence":"first","affiliation":[{"name":"Shanghai Jiao Tong University Affiliated Sixth People's Hospital School of Biomedical Engineering Shanghai Jiao Tong University  1954 Hua Shan Road Shanghai 200030 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