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Stem cells have shown promise in promoting cutaneous wound healing by modulating inflammation, angiogenesis, and re\u2010epithelialization. However, more effective delivery and engraftment strategies are needed to prolong transplanted stem cell lifespan and their pro\u2010healing functions in a chronic wound environment to improve skin regeneration. In this study, an injectable poly(ethylene glycol) (PEG)\u2013gelatin\u2010based hydrogel system is examined to create a functional stem cell niche for the delivery of adipose\u2010derived stem cells (ASCs) into diabetic wounds. Human ASCs are encapsulated into the in situ crosslinked hydrogels and cultured in a 3D topography. The encapsulated cells are well attached and spread inside the hydrogels, retaining viability, proliferation, and metabolic activity up to three weeks in vitro. Allogeneic ASCs are delivered to diabetic wounds by this hydrogel vehicle. It is found that stem cell retention is significantly improved in vivo with vehicle\u2010mediated delivery. The ASC\u2010hydrogel\u2010based treatment decreases inflammatory cell infiltration, enhances neovascularization, and remarkably accelerates wound closure in diabetic mice. Together, these findings suggest this conveniently\u2010applicable ASC\u2010hydrogel\u2010based skin substitute provides a promising potential for the treatment of chronic diabetic wounds.<\/jats:p>","DOI":"10.1002\/adhm.201800432","type":"journal-article","created":{"date-parts":[[2018,7,13]],"date-time":"2018-07-13T10:31:44Z","timestamp":1531477904000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Acceleration of Diabetic Wound Regeneration using an In Situ\u2013Formed Stem\u2010Cell\u2010Based Skin Substitute"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5670-5224","authenticated-orcid":false,"given":"Yixiao","family":"Dong","sequence":"first","affiliation":[{"name":"Shanghai Institute for Advanced Immunochemical Studies ShanghaiTech University  Shanghai 201210 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Surgery Stanford University School of Medicine  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Hyung","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Surgery Stanford University School of Medicine  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Li","sequence":"additional","affiliation":[{"name":"Charles Institute of Dermatology School of Medicine and Medical Science University College Dublin  Dublin 4 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigen","family":"A","sequence":"additional","affiliation":[{"name":"Charles Institute of Dermatology School of Medicine and Medical Science University College Dublin  Dublin 4 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth Anne","family":"Brett","sequence":"additional","affiliation":[{"name":"Department of Surgery Stanford University School of Medicine  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Elvassore","sequence":"additional","affiliation":[{"name":"Shanghai Institute for Advanced Immunochemical Studies ShanghaiTech University  Shanghai 201210 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Charles Institute of Dermatology School of Medicine and Medical Science University College Dublin  Dublin 4 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey C.","family":"Gurtner","sequence":"additional","affiliation":[{"name":"Department of Surgery Stanford University School of Medicine  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,13]]},"reference":[{"key":"e_1_2_8_1_1","unstructured":"IDF Diabetes Atlas 2015 7thed International Diabetes Federation 2015 www.diabetesatlas.org ISBN: 978\u20102\u2010930229\u201081\u20102."},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.130"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009337"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310799"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2007.11.005"},{"key":"e_1_2_8_3_3","doi-asserted-by":"publisher","DOI":"10.1177\/1071100712467436"},{"key":"e_1_2_8_3_4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.293.2.217"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67700-8"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32169"},{"key":"e_1_2_8_4_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2015.12.017"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2014.0607"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.12152"},{"key":"e_1_2_8_5_3","doi-asserted-by":"publisher","DOI":"10.1159\/000381877"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00192"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.4161\/org.27405"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/C1CS15203C"},{"key":"e_1_2_8_9_1","first-page":"7","volume":"3","author":"Leavitt T.","year":"2016","journal-title":"Chronic Wound Care Manag. 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