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Here, a sprayable hydrogel combined with human endometrial organoid extracellular vesicles (HEO\u2010EVs) is developed to enhance uterine function preservation and fertility restoration. The peptide amphiphile hydrogel (labeled CPA) is engineered by conjugating a collagen\u2010binding peptide with glutathione to impart its biocompatible adhesive and antioxidant properties. The therapeutic EVs are isolated and purified from human endometrial organoids that have been stably passaged long\u2010term using a bioreactor\u2010culture system. The resulting HEO\u2010EVs\u2010loaded CPA (CPA@HEO\u2010EVs) rapid gelation, triggered by salt\u2010ion interactions, occurs when the fluid is sprayed onto the uterine lining. The ex vivo studies demonstrate that CPA@HEO\u2010EVs promote cell proliferation, scavenges free radicals, and increases tube formation in human umbilical vein endothelial cells. In vivo experiments further validate that in situ spraying with the CPA@HEO\u2010EVs can promote neovascularization, prevent localized endometrial fibrosis, and effectively enhance fertility in a mouse model of endometrial injury. These findings highlight the promising clinical application of in situ sprayed CPA@HEO\u2010EVs hydrogel for targeted endometrial therapy.<\/jats:p>","DOI":"10.1002\/adhm.202403604","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T03:21:15Z","timestamp":1731986475000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["In Situ Sprayed Hydrogel Delivers Extracellular Vesicles Derived from Human Endometrial Organoids for Uterine Function Preservation and Fertility Restoration"],"prefix":"10.1002","volume":"14","author":[{"given":"Xunsi","family":"Qin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology Peking University Third Hospital  No. 49 North Huayuan Road, Haidian District Beijing 100191 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