{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:02:12Z","timestamp":1791558132334,"version":"4.3.4"},"reference-count":68,"publisher":"Wiley","issue":"39","license":[{"start":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T00:00:00Z","timestamp":1754092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T00:00:00Z","timestamp":1754092800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG086776"],"award-info":[{"award-number":["R01AG086776"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD102184"],"award-info":[{"award-number":["R01HD102184"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Genitourinary syndrome of menopause (GSM) is initiated by the hypoestrogenic state consequent to cessation of ovarian function and involves changes in all vaginal layers. These alterations include decreased epithelial proliferation and differentiation, impaired extracellular matrix (ECM) maintenance, pro\u2010inflammatory immune milieu, and smooth muscle atrophy. Patient satisfaction with existing treatments for GSM is low, due in part to their lack of therapeutic effect throughout all vaginal layers and reliance on hormonal treatments. Decellularized ECM therapeutics are known to facilitate soft tissue repair in a variety of applications. Thus, a porcine vaginal tissue\u2010derived decellularized ECM (vECM) hydrogel suitable for noninvasive topical intravaginal administration is developed specifically for vaginal repair. When applied in a rat model of surgical menopause, vECM significantly improves vaginal epithelial thickness and epithelial stem cell phenotype. Despite topical intravaginal application, vECM is also observed in the lamina propria and fibromuscularis, exerting a regenerative effect on the vaginal smooth muscle layer. Furthermore, vECM modulates macrophage density and promotes pro\u2010regenerative M2\u2010like phenotype within the vaginal tissue. Overall, the work herein demonstrates a new nonhormonal biomaterial treatment that counteracts pathological vaginal alterations \u2013 a hallmark of GSM \u2013 in an established preclinical model of menopause.<\/jats:p>","DOI":"10.1002\/adma.202419977","type":"journal-article","created":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T10:40:36Z","timestamp":1754131236000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Development of a Vaginal Extracellular Matrix Hydrogel for Combating Genitourinary Syndrome of Menopause"],"prefix":"10.1002","volume":"37","author":[{"given":"Emma I.","family":"Zelus","sequence":"first","affiliation":[{"name":"Shu Chien\u2010Gene Lay Department of Bioengineering UC San Diego  La Jolla USA"},{"name":"Sanford Consortium for Regenerative Medicine  La Jolla USA"},{"name":"Sanford Stem Cell Institute UC San Diego  La Jolla USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Grime","sequence":"additional","affiliation":[{"name":"Sanford Consortium for Regenerative Medicine  La Jolla USA"},{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences UC San Diego  La Jolla USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Saviola","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics Anschutz Medical Campus, University of Colorado  Boulder USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxwell","family":"McCabe","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics Anschutz Medical Campus, University of Colorado  Boulder USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk C.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics Anschutz Medical Campus, University of Colorado  Boulder USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Alperin","sequence":"additional","affiliation":[{"name":"Sanford Consortium for Regenerative Medicine  La Jolla USA"},{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences UC San Diego  La Jolla USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6179-898X","authenticated-orcid":false,"given":"Karen L.","family":"Christman","sequence":"additional","affiliation":[{"name":"Shu Chien\u2010Gene Lay Department of Bioengineering UC San Diego  La Jolla USA"},{"name":"Sanford Consortium for Regenerative Medicine  La Jolla USA"},{"name":"Sanford Stem Cell Institute UC San Diego  La Jolla USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,2]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"G.Bachmann R. J.Santen (Ed:R. L. B. A.Chakrabarti) in UpToDate Wolters Kluwer2025."},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.4137\/CMRH.S14498"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5122(95)00968-X"},{"key":"e_1_2_9_4_1","volume-title":"StatPearls","author":"Peacock K.","year":"2023"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.4065\/mcp.2009.0413"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.01.003"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/sm2.17"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2002.124843"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2013.09.003"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12972"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14199"},{"key":"e_1_2_9_12_1","unstructured":"G.Bachmann J. V.Pinkerton in UpToDate Wolters Kluwer 2025."},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S43192"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph18168340"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJWH.S158913"},{"key":"e_1_2_9_15_2","volume":"12","author":"Angelou K.","year":"2020","journal-title":"Cureus"},{"key":"e_1_2_9_15_3","doi-asserted-by":"publisher","DOI":"10.1097\/GME.0000000000001209"},{"key":"e_1_2_9_16_1","volume":"15","author":"Albalawi N. S.","year":"2023","journal-title":"Cureus"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.9b01649"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v023a31"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2017.12.019"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2019.07.012"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2015.03.024"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2018.0180"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40824-023-00348-z"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201500048"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M114.045260"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9BM01963D"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8921284"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijir.3901138"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2008.11.040"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2007.0264"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000000727"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2021.03.070"},{"key":"e_1_2_9_31_2","doi-asserted-by":"publisher","DOI":"10.1088\/1758-5090\/ad95bf"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2014.08.024"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2019.109841"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15776"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2016.01.009"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.36066"},{"key":"e_1_2_9_37_1","first-page":"58","author":"Benini V.","year":"2022","journal-title":"Medicina (Kaunas)"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12144740"},{"key":"e_1_2_9_39_1","author":"Kurobe M.","year":"2020","journal-title":"Abstract 213, ICS 2020"},{"key":"e_1_2_9_39_2","doi-asserted-by":"publisher","DOI":"10.56499\/jppres22.1512_11.1.110"},{"key":"e_1_2_9_39_3","doi-asserted-by":"publisher","DOI":"10.4111\/icu.20200513"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2023.100589"},{"key":"e_1_2_9_40_2","doi-asserted-by":"crossref","DOI":"10.1177\/20595131211038313","volume":"8","author":"Petrie K.","year":"2022","journal-title":"Scars Burn Heal"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2008.0419"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.12.035"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202300782"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2016.0304"},{"key":"e_1_2_9_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.06.060"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.0317"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0TB01885F"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.engreg.2023.05.001"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29143"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2023.2290940"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2024.122545"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2019.11.012"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.03.054"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2024.04.019"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izad270"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-018-0096-2"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.14053"},{"key":"e_1_2_9_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fmre.2023.12.015"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.5123"},{"key":"e_1_2_9_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1322"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4256"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202419977","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adma.202419977","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.202419977","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T05:59:20Z","timestamp":1771394360000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.202419977"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,2]]},"references-count":68,"journal-issue":{"issue":"39","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/adma.202419977"],"URL":"https:\/\/doi.org\/10.1002\/adma.202419977","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,2]]},"assertion":[{"value":"2024-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2419977"}}