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Puerarin (PUE) exhibits potent anti-fibrotic activity. Herein, we fabricated a PUE-loaded peptide hydrogel (PUE-Gel) and investigated its physicochemical properties, biocompatibility, and therapeutic efficacy against IUA, as well as the underlying mechanism. PUE-Gel exhibited excellent biocompatibility, injectability, sustained drug release, and biodegradability. In an in vivo IUA model, PUE-Gel significantly restored injured endometrial morphology, increased gland and blood vessel numbers, and attenuated fibrosis in IUA rats. It also restored the expression of estrogen\/progesterone receptors and integrin \u03b1\u03bd\u03b23 to improve endometrial receptivity, along with a markedly enhanced pregnancy rate. Transcriptomic and mechanistic studies suggested that the injury-activated Wnt\/\u03b2-catenin signaling pathway may contribute to endometrial fibrosis. Collectively, PUE-Gel acts as both a physical anti-adhesion barrier and a localized sustained drug delivery system, effectively alleviating IUA potentially through modulation of the Wnt\/\u03b2-catenin pathway to promote endometrial regeneration, angiogenesis, and fertility recovery. This work provides a bioactive hydrogel biomaterial and a promising potential strategy for IUA and endometrial damage-induced infertility.<\/jats:p>","DOI":"10.1021\/acsami.6c12025","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:01:44Z","timestamp":1792076504000},"page":"57068-57080","source":"Crossref","is-referenced-by-count":0,"title":["Puerarin-Loaded Peptide Hydrogel Restores Endometrial Function and Fertility in Intrauterine Adhesion"],"prefix":"10.1021","volume":"18","author":[{"given":"Yixin","family":"Liang","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital, Wenzhou Medical University , , , ,","place":["Wenzhou, Zhejiang Province, P. R. China, 325035"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Xie","sequence":"additional","affiliation":[{"name":"Huzhou Central Hospital, The Fifth School of Clinical Medicine of Zhejiang Chinese Medical University , , ,","place":["Huzhou, Zhejiang Province, P. R. China, 313000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqiang","family":"Lu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Wenzhou Medical University , , , ,","place":["Wenzhou, Zhejiang Province, P. R. China, 325035"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wenzhou Medical University , , ,","place":["Wenzhou, Zhejiang Province, P. R. China, 325035"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Wu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Wenzhou Medical University , , , ,","place":["Wenzhou, Zhejiang Province, P. R. China, 325035"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghao","family":"Shen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Wenzhou Medical University , , , ,","place":["Wenzhou, Zhejiang Province, P. R. China, 325035"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Wenzhou Medical University , , ,","place":["Wenzhou, Zhejiang Province, P. R. 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