{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:53:42Z","timestamp":1790999622245,"version":"4.1.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Key Research and Development Program of Shandong Province, China","award":["2023CXGC010505"],"award-info":[{"award-number":["2023CXGC010505"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101698"],"award-info":[{"award-number":["82101698"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yantai Science and Technology Innovation Development Plan Project","award":["2024YD045"],"award-info":[{"award-number":["2024YD045"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Following injury from medical procedures or infections, the endometrium may fail to regenerate, leading to the formation of scar tissue that results in intrauterine adhesion, potentially disrupting normal endometrial function and contributing to infertility. Regenerative medicine is regarded as a promising solution to this concern, potentially providing effective treatment methods for the regeneration of injured human endometrium. Herein, we fabricated a degradable endometrial repair membrane (DERM) mainly composed of extracellular matrix, which acts as an intrauterine physical barrier and supports endometrial regeneration. In this study, we explored the role of DERM in epithelial transformation, anti-fibrosis, and angiogenesis using both an in vitro cell model and an in vivo electrothermal-induced rabbit intrauterine adhesion (IUA) model. In vitro, the DERM effectively reduced the expression of fibrosis markers (FN1, COL1A1, and \u03b1-SMA) while promoting the expression of epithelial-related markers (CDH1 and CK19) in primary human endometrial stromal cells and angiogenesis-related factors (VEGFA and VEGFR2) in HUVECSs. The rabbit electrothermal injury model was used to mimic clinical electrosurgical adhesiolysis. In vivo, HE staining revealed DERM significantly accelerated endometrial regeneration, angiogenesis, and restored uterine functionality; Masson staining confirmed the deposition of collagen in endometrium of rabbits was notably reduced following the DERM treatment. Moreover, DERM remarkably upregulated CDH1 and CK19 expression, and gradually degraded in the uterine cavity to avoid inflammatory irritation. In conclusion, the DERM facilitated the repair and regeneration of the endometrium, suggesting a promising new therapeutic approach for endometrial repair.<\/jats:p>","DOI":"10.1093\/biolre\/ioag151","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:22:12Z","timestamp":1784546532000},"source":"Crossref","is-referenced-by-count":0,"title":["Degradable endometrial repair membrane promoted the endometrial regeneration in intrauterine adhesions therapy"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3105-4816","authenticated-orcid":false,"given":"Huishan","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine, the Affiliated Yantai Yuhuangding Hospital of Qingdao University , Yantai ,","place":["China"]},{"name":"Shandong Provincial Key Medical and Health Laboratory of Reproductive Health and Genetics (Yantai Yuhuangding Hospital) , Yantai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunzhi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, the Affiliated Yantai Yuhuangding Hospital of Qingdao University , Yantai ,","place":["China"]},{"name":"Shandong Provincial Key Medical and Health Laboratory of Reproductive Health and Genetics (Yantai Yuhuangding Hospital) , Yantai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Neo Modulus (Shandong) Medical Sci-Tech Co., Ltd. , Weifang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingwei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, the Affiliated Yantai Yuhuangding Hospital of Qingdao University , Yantai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchu","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, the Affiliated Yantai Yuhuangding Hospital of Qingdao University , Yantai ,","place":["China"]},{"name":"Shandong Provincial Key Medical and Health Laboratory of Reproductive Health and Genetics (Yantai Yuhuangding Hospital) , Yantai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"2026100223063061600_ref1","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.rbmo.2010.11.018","article-title":"Management of Asherman\u2019s syndrome","volume":"23","author":"March","year":"2011","journal-title":"Reprod Biomed Online"},{"key":"2026100223063061600_ref2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.jconrel.2019.12.007","article-title":"Therapeutic options and drug delivery strategies for the prevention of intrauterine adhesions","volume":"318","author":"Kou","year":"2020","journal-title":"J Control Release"},{"key":"2026100223063061600_ref3","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1093\/humrep\/deaa289","article-title":"Reproductive performance of women with and without intrauterine adhesions following recurrent dilatation and curettage for miscarriage: long-term follow-up of a randomized controlled trial","volume":"36","author":"Hooker","year":"2021","journal-title":"Hum Reprod"},{"key":"2026100223063061600_ref4","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.jdent.2008.02.017","article-title":"Routine oral examinations in primary care: which predictors determine what is done? A prospective clinical case recording study","volume":"36","author":"Mettes","year":"2008","journal-title":"J Dent"},{"key":"2026100223063061600_ref5","doi-asserted-by":"crossref","first-page":"e13262","DOI":"10.1111\/aji.13262","article-title":"Transforming growth factor-beta1 in intrauterine adhesion","volume":"84","author":"Abudukeyoumu","year":"2020","journal-title":"Am J Reprod Immunol"},{"key":"2026100223063061600_ref6","doi-asserted-by":"publisher","first-page":"4158287","DOI":"10.1155\/2016\/4158287","article-title":"Role of transforming growth factor-beta1 and Smads signaling pathway in intrauterine adhesion","volume":"2016","author":"Salma","year":"2016","journal-title":"Mediators Inflamm"},{"key":"2026100223063061600_ref7","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.fertnstert.2008.02.096","article-title":"Asherman syndrome--one century later","volume":"89","author":"Yu","year":"2008","journal-title":"Fertil Steril"},{"key":"2026100223063061600_ref8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s00281-024-01030-9","article-title":"Mechanistic insights into intrauterine adhesions","volume":"47","author":"Zhao","year":"2024","journal-title":"Semin Immunopathol"},{"key":"2026100223063061600_ref9","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/s13287-019-1332-8","article-title":"Exosomes derived from mesenchymal stem cells reverse EMT via TGF-beta1\/Smad pathway and promote repair of damaged endometrium","volume":"10","author":"Yao","year":"2019","journal-title":"Stem Cell Res Ther"},{"key":"2026100223063061600_ref10","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/s41419-020-2666-y","article-title":"DeltaNp63alpha-induced DUSP4\/GSK3beta\/SNAI1 pathway in epithelial cells drives endometrial fibrosis","volume":"11","author":"Zhao","year":"2020","journal-title":"Cell Death Dis"},{"key":"2026100223063061600_ref11","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaaa074","article-title":"HMGA2-induced epithelial-mesenchymal transition is reversed by let-7d in intrauterine adhesions","volume":"27","author":"Song","year":"2021","journal-title":"Mol Hum Reprod"},{"key":"2026100223063061600_ref12","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s40824-021-00242-6","article-title":"Recent trends in therapeutic strategies for repairing endometrial tissue in intrauterine adhesion","volume":"25","author":"Ma","year":"2021","journal-title":"Biomater Res"},{"key":"2026100223063061600_ref13","doi-asserted-by":"publisher","first-page":"100101","DOI":"10.1016\/j.mtbio.2021.100101","article-title":"Recent developments in bio-scaffold materials as delivery strategies for therapeutics for endometrium regeneration","volume":"11","author":"Li","year":"2021","journal-title":"Mater Today Bio"},{"key":"2026100223063061600_ref14","doi-asserted-by":"publisher","first-page":"100389","DOI":"10.1016\/j.mtbio.2022.100389","article-title":"Research progress of stem cell therapy for endometrial injury","volume":"16","author":"Cen","year":"2022","journal-title":"Mater Today Bio"},{"key":"2026100223063061600_ref15","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.biopha.2018.03.091","article-title":"Stem cell therapy in Asherman syndrome and thin endometrium: stem cell- based therapy","volume":"102","author":"Azizi","year":"2018","journal-title":"Biomed Pharmacother"},{"key":"2026100223063061600_ref16","doi-asserted-by":"crossref","first-page":"1264006","DOI":"10.3389\/fbioe.2023.1264006","article-title":"Treatment strategies for intrauterine adhesion: focus on the exosomes and hydrogels","volume":"11","author":"Wu","year":"2023","journal-title":"Front Bioeng Biotechnol"},{"key":"2026100223063061600_ref17","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.actbio.2015.08.044","article-title":"Core-shell PVA\/gelatin electrospun nanofibers promote human umbilical vein endothelial cell and smooth muscle cell proliferation and migration","volume":"27","author":"Merkle","year":"2015","journal-title":"Acta Biomater"},{"key":"2026100223063061600_ref18","doi-asserted-by":"publisher","first-page":"2590","DOI":"10.1002\/jbm.b.34591","article-title":"In vitro biocompatibility of biohybrid polymers membrane evaluated in human gingival fibroblasts","volume":"108","author":"Guo","year":"2020","journal-title":"J Biomed Mater Res B Appl Biomater"},{"key":"2026100223063061600_ref19","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jbm.a.36676","article-title":"In vivo evaluation of an electrospun gelatin nonwoven mat for regeneration of epithelial tissues","volume":"107","author":"Strassburg","year":"2019","journal-title":"J Biomed Mater Res A"},{"key":"2026100223063061600_ref20","doi-asserted-by":"publisher","first-page":"482","DOI":"10.11817\/j.issn.1672-7347.2025.240529","article-title":"Effect of different surgical approaches for intrauterine adhesions patients on pregnancy outcomes","volume":"50","author":"Guo","year":"2025","journal-title":"Zhong Nan Da Xue Xue Bao Yi Xue Ban"},{"key":"2026100223063061600_ref21","doi-asserted-by":"publisher","first-page":"2422","DOI":"10.1093\/humrep\/dead196","article-title":"The humanin analogue (HNG) alleviates intrauterine adhesions by inhibiting endometrial epithelial cells ferroptosis: a rat model-based study","volume":"38","author":"Zou","year":"2023","journal-title":"Hum Reprod"},{"key":"2026100223063061600_ref22","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1186\/s13287-020-01990-3","article-title":"si-SNHG5-FOXF2 inhibits TGF-beta1-induced fibrosis in human primary endometrial stromal cells by the Wnt\/beta-catenin signalling pathway","volume":"11","author":"Liu","year":"2020","journal-title":"Stem Cell Res Ther"},{"key":"2026100223063061600_ref23","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/s10456-010-9178-9","article-title":"Imaging of angiogenesis","volume":"13","author":"Mulder","year":"2010","journal-title":"Angiogenesis"},{"key":"2026100223063061600_ref24","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.jmig.2013.07.018","article-title":"Efficacy of estrogen therapy in patients with intrauterine adhesions: systematic review","volume":"21","author":"Johary","year":"2014","journal-title":"J Minim Invasive Gynecol"},{"key":"2026100223063061600_ref25","article-title":"Focus on the primary prevention of intrauterine adhesions: current concept and vision","volume":"22","author":"Lee","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2026100223063061600_ref26","doi-asserted-by":"publisher","first-page":"2627","DOI":"10.7150\/ijbs.69410","article-title":"Organoid transplantation can improve reproductive prognosis by promoting endometrial repair in mice","volume":"18","author":"Zhang","year":"2022","journal-title":"Int J Biol Sci"},{"key":"2026100223063061600_ref27","doi-asserted-by":"crossref","DOI":"10.1007\/s11427-024-2842-6","article-title":"Development of regenerative therapies targeting fibrotic endometrium in intrauterine adhesion or thin endometrium to restore uterine function","volume":"68","author":"Zhao","year":"2025","journal-title":"Sci China Life Sci"},{"key":"2026100223063061600_ref28","doi-asserted-by":"publisher","first-page":"963689720952055","DOI":"10.1177\/0963689720952055","article-title":"Transplantation of human adipose stem cells using acellular human amniotic membrane improves angiogenesis in injured endometrial tissue in a rat intrauterine adhesion model","volume":"29","author":"Han","year":"2020","journal-title":"Cell Transplant"},{"key":"2026100223063061600_ref29","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s13287-019-1179-z","article-title":"Transplantation of oral mucosal epithelial cells seeded on decellularized and lyophilized amniotic membrane for the regeneration of injured endometrium","volume":"10","author":"Chen","year":"2019","journal-title":"Stem Cell Res Ther"},{"key":"2026100223063061600_ref30","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1093\/humupd\/dmae013","article-title":"Evolution of biotechnological advances and regenerative therapies for endometrial disorders: a systematic review","volume":"30","author":"Rodriguez-Eguren","year":"2024","journal-title":"Hum Reprod Update"},{"key":"2026100223063061600_ref31","doi-asserted-by":"publisher","first-page":"140220","DOI":"10.1016\/j.ijbiomac.2025.140220","article-title":"Therapeutic strategies: bioactive hydrogels oxidized sodium alginate\/strontium\/betamethasone for preventing intrauterine adhesion","volume":"300","author":"Wu","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"2026100223063061600_ref32","doi-asserted-by":"publisher","first-page":"122615","DOI":"10.1016\/j.biomaterials.2024.122615","article-title":"Locationally activated PRP via an injectable dual-network hydrogel for endometrial regeneration","volume":"309","author":"Qi","year":"2024","journal-title":"Biomaterials"},{"key":"2026100223063061600_ref33","doi-asserted-by":"publisher","first-page":"122923","DOI":"10.1016\/j.biomaterials.2024.122923","article-title":"Ru single-atom nanozymes targeting ROS-ferroptosis pathways for enhanced endometrial regeneration in intrauterine adhesion therapy","volume":"315","author":"Liang","year":"2025","journal-title":"Biomaterials"},{"key":"2026100223063061600_ref34","doi-asserted-by":"publisher","first-page":"6499","DOI":"10.1021\/acsnano.4c17645","article-title":"Multiresponsive microcapsules for prevention of intrauterine adhesion","volume":"19","author":"Wang","year":"2025","journal-title":"ACS Nano"},{"key":"2026100223063061600_ref35","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1186\/s12951-024-02780-2","article-title":"Thermosensitive hydrogel as a sustained release carrier for mesenchymal stem cell-derived extracellular vesicles in the treatment of intrauterine adhesion","volume":"22","author":"Yu","year":"2024","journal-title":"J Nanobiotechnology"},{"key":"2026100223063061600_ref36","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.1038\/s41591-020-1040-z","article-title":"Single-cell transcriptomic atlas of the human endometrium during the menstrual cycle","volume":"26","author":"Wang","year":"2020","journal-title":"Nat Med"},{"key":"2026100223063061600_ref37","doi-asserted-by":"crossref","first-page":"5890","DOI":"10.1038\/s41467-023-41656-1","article-title":"Decoding the endometrial niche of Asherman's syndrome at single-cell resolution","volume":"14","author":"Santamaria","year":"2023","journal-title":"Nat Commun"},{"key":"2026100223063061600_ref38","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26094183","article-title":"Endometrial stromal senescence mediates the progression of intrauterine adhesions","volume":"26","author":"Deryabin","year":"2025","journal-title":"Int J Mol Sci"},{"key":"2026100223063061600_ref39","doi-asserted-by":"publisher","first-page":"e17601","DOI":"10.15252\/emmm.202317601","article-title":"Targeting CD301(+) macrophages inhibits endometrial fibrosis and improves pregnancy outcome","volume":"15","author":"Lv","year":"2023","journal-title":"EMBO Mol Med"},{"key":"2026100223063061600_ref40","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1631\/jzus.B1700086","article-title":"Creation of a rabbit model for intrauterine adhesions using electrothermal injury","volume":"19","author":"Xu","year":"2018","journal-title":"J Zhejiang Univ Sci B"},{"key":"2026100223063061600_ref41","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41420-025-02377-0","article-title":"Endothelial senescence induced by PAI-1 promotes endometrial fibrosis","volume":"11","author":"Wu","year":"2025","journal-title":"Cell Death Discov"},{"key":"2026100223063061600_ref42","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.actbio.2023.06.013","article-title":"Functionalized human umbilical cord mesenchymal stem cells and injectable HA\/gel hydrogel synergy in endometrial repair and fertility recovery","volume":"167","author":"Zhang","year":"2023","journal-title":"Acta Biomater"},{"key":"2026100223063061600_ref43","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1093\/humupd\/dmad004","article-title":"Angiogenesis in abnormal uterine bleeding: a narrative review","volume":"29","author":"Middelkoop","year":"2023","journal-title":"Hum Reprod Update"},{"key":"2026100223063061600_ref44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12951-020-00755-7","article-title":"Nanocomposite scaffolds for accelerating chronic wound healing by enhancing angiogenesis","volume":"19","author":"Nosrati","year":"2021","journal-title":"J Nanobiotechnology"},{"key":"2026100223063061600_ref45","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1186\/s13287-025-04298-2","article-title":"Human embryonic stem cell-derived immunity-and-matrix-regulatory cells promote endometrial repair and fertility restoration in IUA rats","volume":"16","author":"Cao","year":"2025","journal-title":"Stem Cell Res Ther"},{"key":"2026100223063061600_ref46","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.freeradbiomed.2023.06.001","article-title":"Ferroptosis contributes to endometrial fibrosis in intrauterine adhesions","volume":"205","author":"Zhu","year":"2023","journal-title":"Free Radic Biol Med"},{"key":"2026100223063061600_ref47","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1146\/annurev-cellbio-011723-021442","article-title":"Mechanisms of regeneration and fibrosis in the endometrium","volume":"39","author":"Ang","year":"2023","journal-title":"Annu Rev Cell Dev Biol"},{"key":"2026100223063061600_ref48","first-page":"11:e77663","article-title":"Single-cell RNA sequencing and lineage tracing confirm mesenchyme to epithelial transformation (MET) contributes to repair of the endometrium at menstruation","author":"Kirkwood","year":"2022","journal-title":"Elife"},{"key":"2026100223063061600_ref49","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1186\/s12964-024-01656-0","article-title":"Human amnion mesenchymal stem cells promote endometrial repair via paracrine, preferentially than transdifferentiation","volume":"22","author":"Huang","year":"2024","journal-title":"Cell Commun Signal"}],"container-title":["Biology of Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/biolreprod\/advance-article-pdf\/doi\/10.1093\/biolre\/ioag151\/69707376\/ioag151.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/advance-article-pdf\/doi\/10.1093\/biolre\/ioag151\/69707376\/ioag151.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:06:47Z","timestamp":1790996807000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biolreprod\/advance-article\/doi\/10.1093\/biolre\/ioag151\/8739308"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":49,"URL":"https:\/\/doi.org\/10.1093\/biolre\/ioag151","relation":{},"ISSN":["0006-3363","1529-7268"],"issn-type":[{"value":"0006-3363","type":"print"},{"value":"1529-7268","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]},"article-number":"ioag151"}}