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Currently, human endometrium\u2010derived adventitial cells (En\u2010ADVs) are considered ideal seed cells with high pluripotency for regenerative medicine. However, critical issues such as noninvasive repair of tissues, targeting of native stem cells, and continuous action in the injured sites are not well resolved. Herein, En\u2010ADV spheroid\u2010loaded hierarchical microneedles (MN\/En\u2010ADV) for in situ intrauterine repair are developed. The flexible microneedles are fabricated with gelatin methacryloyl and lactoferrin, imparting the characteristics of rapid degradation and antimicrobial activity. Benefiting from an array of microwells on microneedles, En\u2010ADVs can rapidly form 3D cell spheroids, which display higher potential for cell proliferation, differentiation, and migration than dissociated cells. With the application of MN\/En\u2010ADV, the repaired uteri show well\u2010defined myometrial regeneration, angiogenesis, and an increase of endometrial receptivity in a rat AS model. Notably, embryos are able to implant in the reconstructed sites and remain viable, indicating that this system promotes the restoration of both normal morphology and reproductive function in the injured uterus. It is anticipated that multifunctional MN\/En\u2010ADV can be an ideal candidate for versatile in situ tissue regeneration.<\/jats:p>","DOI":"10.1002\/smll.202201225","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T19:40:00Z","timestamp":1657222800000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Human Endometrium\u2010Derived Adventitial Cell Spheroid\u2010Loaded Antimicrobial Microneedles for Uterine Regeneration"],"prefix":"10.1002","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6253-5885","authenticated-orcid":false,"given":"Shiyuan","family":"Li","sequence":"first","affiliation":[{"name":"Center for Reproductive Medicine and Obstetrics and Gynecology The Affiliated Drum Tower Hospital of Nanjing University Medical School  Nanjing 210008 China"},{"name":"Center for Molecular Reproductive Medicine Nanjing University  Nanjing 210008 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Tower Hospital of Nanjing University Medical School  Nanjing 210008 China"},{"name":"Center for Molecular Reproductive Medicine Nanjing University  Nanjing 210008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanming","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine and Obstetrics and Gynecology The Affiliated Drum Tower Hospital of Nanjing University Medical School  Nanjing 210008 China"},{"name":"Center for Molecular Reproductive Medicine Nanjing University  Nanjing 210008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialian","family":"Mao","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine and Obstetrics and Gynecology The Affiliated Drum Tower Hospital of Nanjing University Medical School  Nanjing 210008 China"},{"name":"Center for Molecular Reproductive Medicine Nanjing University  Nanjing 210008 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Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou Zhejiang 325001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery The Affiliated Drum Tower Hospital of Nanjing University Medical School  Nanjing 210008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6330-7945","authenticated-orcid":false,"given":"Lijun","family":"Ding","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine and Obstetrics and Gynecology The Affiliated Drum Tower Hospital of Nanjing University Medical School  Nanjing 210008 China"},{"name":"Center for Molecular Reproductive Medicine Nanjing University  Nanjing 210008 China"},{"name":"Center for Clinical Stem Cell Research The Affiliated Drum Tower Hospital of Nanjing University Medical School  Nanjing 210008 China"},{"name":"State Key Laboratory of Analytic Chemistry for Life Science Nanjing University  Nanjing Jiangsu 210093 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,7]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2008.02.096"},{"key":"e_1_2_9_2_1","volume-title":"StatPearls","author":"Smikle C.","year":"2022"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-012-9221-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.03.091"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.02.046"},{"key":"e_1_2_9_6_1","first-page":"145","volume":"36","author":"Zhu X.","year":"2020","journal-title":"Hum. 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