{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T07:47:36Z","timestamp":1794037656375,"version":"4.8.0"},"reference-count":72,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T00:00:00Z","timestamp":1729814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Early hyper\u2010inflammation caused by intrauterine injury triggered subsequent intrauterine adhesion (IUA). STAT1\u2010mediated M1 macrophages are confirmed to secrete pro\u2010inflammatory cytokines to accelerate inflammatory cascade and IUA formation by multi\u2010omics analysis and experimental verification. However, clinically used hyaluronic acid (HA) hydrogels are prone to slip out of injury sites due to poor bio\u2010adhesion properties. Therefore, there are still challenges in applying hydrogels for M1 macrophage intervention in IUA treatment. Herein, an engineered extracellular vesicles (EVs) hybrid snail mucus (SM)\u2010enhanced adhesive hydrogels to improve bio\u2010adhesion property is fabricated and M1 macrophage intervention through targeting delivery and STAT1 silencing is achieved. First, inspired by the high bio\u2010adhesion capacity of SM, SM and gelatin methacrylate (GelMA) solution are mixed to construct GelMA\/SM (GS) hydrogel. Then, folic acid\u2010modified extracellular vesicles (FA\u2010EVs) are synthesized for targeting the delivery of STAT1\u2010siRNA. Upon injection of FA\u2010EVs hybrid GS hydrogel into the uterine cavity, a protective hydrogel layer forms on the surface of injury sites and sustains the release of STAT1\u2010siRNA\u2010loaded FA\u2010EVs to curtail M1 macrophages generation through inhibiting STAT1 phosphorylation, resulting in reduction of myofibroblasts activation and collagen deposition. In addition, the pregnancy rate and the number of fetuses in rats treated with this hydrogel were much higher than those in other groups, suggesting that the hydrogel could promote functional endometrial regeneration and restore fertility. Overall, this study presents a promising strategy for employing FA\u2010EVs hybrid adhesive hydrogel with superior bio\u2010adhesion properties and M1 macrophage targeting delivery for IUA treatment and uterus recovery.<\/jats:p>","DOI":"10.1002\/advs.202410769","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T15:54:51Z","timestamp":1729871691000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Gene Therapy for Inflammatory Cascade in Intrauterine Injury with Engineered Extracellular Vesicles Hybrid Snail Mucus\u2010enhanced Adhesive Hydrogels"],"prefix":"10.1002","volume":"12","author":[{"given":"Xiaotong","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Gynecology Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal\u2010Fetal Medicine and Gynecologic Oncology Shanghai First Maternity and Infant Hospital School of Medicine Tongji University  Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gynecology Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal\u2010Fetal Medicine and Gynecologic Oncology Shanghai First Maternity and Infant Hospital School of Medicine Tongji University  Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Hematology Huashan Hospital Fudan University  Shanghai 200040 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Gynecology Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal\u2010Fetal Medicine and Gynecologic Oncology Shanghai First Maternity and Infant Hospital School of Medicine Tongji University  Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Gynecology Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal\u2010Fetal Medicine and Gynecologic Oncology Shanghai First Maternity and Infant Hospital School of Medicine Tongji University  Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pusheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gynecology Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal\u2010Fetal Medicine and Gynecologic Oncology Shanghai First Maternity and Infant Hospital School of Medicine Tongji University  Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gynecology Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal\u2010Fetal Medicine and Gynecologic Oncology Shanghai First Maternity and Infant Hospital School of Medicine Tongji University  Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gynecology Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal\u2010Fetal Medicine and Gynecologic Oncology Shanghai First Maternity and Infant Hospital School of Medicine Tongji University  Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Gynecology Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal\u2010Fetal Medicine and Gynecologic Oncology Shanghai First Maternity and Infant Hospital School of Medicine Tongji University  Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology  Macao 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5151-6176","authenticated-orcid":false,"given":"Shuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Gynecology Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal\u2010Fetal Medicine and Gynecologic Oncology Shanghai First Maternity and Infant Hospital School of Medicine Tongji University  Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,25]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204969"},{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1264006"},{"key":"e_1_2_8_1_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.12.007"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-020-00343-y"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-011723-021442"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202106510"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2019.03.003"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2008.02.096"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2014.10.032"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7292(03)00030-4"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-013-2838-4"},{"key":"e_1_2_8_7_1","first-page":"6","author":"Lingjuan W.","year":"2020","journal-title":"Sci. Adv."},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40824-021-00242-6"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-35907-4"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202149174"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2023.104156"},{"key":"e_1_2_8_10_3","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c10884"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compositesb.2023.110520"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202104112"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16070964"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.022"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07201"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.616893"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.108944"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0029-z"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2009.04.023"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202311964"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115284"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2012.08.008"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01382-y"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2019.03.034"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120390"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2020.09.014"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-023-00878-9"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c04206"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm990017d"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.04.023"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.06.027"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c03556"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2023.104854"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-06-1792"},{"key":"e_1_2_8_28_1","first-page":"38","author":"Shaun S.","year":"2013","journal-title":"Immunity"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-021-00867-7"},{"key":"e_1_2_8_28_3","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12072"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0383-0"},{"key":"e_1_2_8_30_1","volume":"2019","author":"Min Z.","year":"2019","journal-title":"Mediators Inflamm."},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120390"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2020.09.014"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-021-00439-4"},{"key":"e_1_2_8_34_1","first-page":"186","volume":"16","author":"Yao X.","year":"2024","journal-title":"Nanomicro. Lett"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.0c00249"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2022.114113"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1807"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22341"},{"key":"e_1_2_8_39_1","first-page":"18","author":"Huidong L.","year":"2024","journal-title":"ACS Nano"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-019-00112-6"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-35907-4"},{"key":"e_1_2_8_42_1","first-page":"21","volume":"36","author":"Huijun S.","year":"2024","journal-title":"Adv. Mater."},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-327183"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.913007"},{"key":"e_1_2_8_44_2","doi-asserted-by":"publisher","DOI":"10.1039\/D1FO03768D"},{"key":"e_1_2_8_44_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04802-z"},{"key":"e_1_2_8_45_1","first-page":"21","volume":"36","author":"Sun H.","year":"2024","journal-title":"Adv. Mater."},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar2971"},{"key":"e_1_2_8_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.03.021"},{"key":"e_1_2_8_46_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01070-3"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202317601"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2023.143144"},{"key":"e_1_2_8_49_1","first-page":"21","volume":"36","author":"Sun H. J.","year":"2024","journal-title":"Adv. Mater."},{"key":"e_1_2_8_50_1","author":"Th\u00e9ry C.","year":"2006","journal-title":"Curr Protoc Cell Biol"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2023.2182254"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2023.03.013"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202410769","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T21:07:06Z","timestamp":1767042426000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202410769"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,25]]},"references-count":72,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/advs.202410769"],"URL":"https:\/\/doi.org\/10.1002\/advs.202410769","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,25]]},"assertion":[{"value":"2024-09-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2410769"}}