{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:35:37Z","timestamp":1785216937349,"version":"3.55.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":170,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Zhejiang Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["LZ23H040001"],"award-info":[{"award-number":["LZ23H040001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Summit Advancement Disciplines of Zhejiang Province"},{"name":"Wenzhou Medical University\u2014Pharmaceutics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>A healthy endometrium is crucial for embryo implantation and pregnancy maintenance. Thin endometrium, reduced glands and fibrosis resulting from infection or mechanical injury, are the primary causes of long-term infertility and poor pregnancy outcomes. Unfortunately, these issues have not been resolved by conventional clinical methods. Keratinocyte growth factor-2 (KGF-2) is an epithelial mitogen that regulates proliferation and migration of epithelial cells. Nitric oxide (NO) is involved in maintaining vascular homeostasis and angiogenesis. Poloxamer-407 (P) hydrogel is a promising topical drug delivery system due to its excellent solution-gel transition properties in response to body temperature. In this study, therapeutic NO gas was first prepared into stabilized microbubbles (NO-MBs). Subsequently, KGF-2 and NO-MBs were encapsulated into micelles of P hydrogel to form a multifunctional temperature-sensitive (28.9\u201331.8\u00b0C) hydrogel (KGF-NO-MBs-P hydrogel). This hydrogel not only exhibited suitable apparent viscosity, bio-adhesive and mechanical properties for application in situ but also showed sustained release of KGF-2 and NO. In vivo, KGF-NO-MBs-P hydrogel effectively restored endometrial morphology, increased the number of glands and endometrial thickness, reversed endometrial fibrosis and improved pregnancy outcomes by synergistic regulation of KGF-2 and NO. Repair of endometrial injury was closely related to promoting neovascularization, inducing endometrial cell proliferation and epithelialization, inhibiting apoptosis and inflammation and balancing collagen subtypes. Therefore, KGF-NO-MBs-P hydrogel may be useful in promoting endometrial regeneration and fertility restoration through in situ microinjection. This study represented a convenient, safe and promising method for repair of endometrial injury.<\/jats:p>","DOI":"10.1093\/rb\/rbaf062","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T18:17:41Z","timestamp":1751048261000},"source":"Crossref","is-referenced-by-count":5,"title":["Two-in-one: multifunctional poloxamer hydrogel accelerates endometrial regeneration and fertility restoration through synergistic regulation of KGF-2 and NO"],"prefix":"10.1093","volume":"12","author":[{"given":"Yijia","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou 325000,","place":["China"]},{"name":"Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinji","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuitao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"2025072415070396600_rbaf062-B1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/s13287-024-03788-z","article-title":"Restoration of functional endometrium in an intrauterine adhesion rat model with endometrial stromal cells transplantation","volume":"15","author":"Zhengli","year":"2024","journal-title":"Stem Cell Res Ther"},{"key":"2025072415070396600_rbaf062-B2","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1186\/s13287-022-02860-w","article-title":"Treating intrauterine 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