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This study presents a directly translatable strategy for treating intrauterine adhesions (IUA) using a clinical\u2010grade, injectable fibrin hydrogel (Porcine Fibrin Sealant, PFS) to deliver MSCs\/EVs. This platform not only ensures biocompatibility and surgical handling but also provides a protective niche. In rat models of mechanically\u2010 and ethanol\u2010induced IUA, optimal\u2010dose PFS\u2010MSCs injected into the uterine cavity promote endometrial regeneration, as shown by increased endometrial thickness, gland number, and reduced fibrosis. This treatment further restores reproductive function, as evidenced by the enhanced secretion of fertility\u2010related factors, improved embryo implantation, and the live birth of healthy offspring. Mechanistically, transcriptomic and histological analyses of the PFS\u2010MSCs treated group revealed dual repair mechanisms: (1) immune remodeling, characterized by decreased M1 macrophages, enhanced M2 macrophage polarization, expanded Treg populations, and upregulated IL\u20104 level, and (2) tissue regeneration, marked by upregulated bFGF level, increased angiogenesis, and enhanced cell proliferation. Crucially, the cell\u2010free PFS\u2010EVs strategy achieved therapeutic equivalence to the PFS\u2010MSCs strategy, fully reversing ethanol\u2010induced IUA damage and enabling fertility recovery. This safe and effective platform presents a directly translatable strategy for IUA treatment.<\/jats:p>","DOI":"10.1002\/adhm.202504360","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T12:50:37Z","timestamp":1770641437000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An Injectable Clinical\u2010Grade Fibrin Hydrogel Restores Fertility in Intrauterine Adhesions via MSC\u2010Mediated Immune and Regenerative Modulation, Unlocking an Equivalent Cell\u2010Free EV\u2010Based Therapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Yixin","family":"Zhang","sequence":"first","affiliation":[{"name":"Translational Research Centre of Regenerative Medicine and 3D Printing Department of Orthopedic Surgery Guangzhou Key Laboratory of Spine Disease Prevention and Treatment Guangdong Province Engineering Research Center For Biomedical Engineering State Key Laboratory of Respiratory Disease Guangdong Provincial Key Laboratory of Major Obstetric Diseases Guangdong Provincial Clinical Research Center For Obstetrics and Gynecology The Third Affiliated Hospital Guangzhou Medical University  Guangzhou..."},{"name":"Research Center for Clinical and Translational Medicine Huazhong University of Science and Technology Union Shenzhen Hospital Shenzhen Nanshan People's Hospital, and the Sixth Affiliated Hospital of Shenzhen University Medical School  Shenzhen P. 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