{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:30:07Z","timestamp":1771929007244,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011576","name":"Inonu University","doi-asserted-by":"publisher","award":["TOA-2024-3403"],"award-info":[{"award-number":["TOA-2024-3403"]}],"id":[{"id":"10.13039\/501100011576","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: This study introduces an experimental model of a large, full-thickness skin defect and evaluates how adipose-derived stem cells characterized by high self-renewal and differentiation capacity affect both wound healing and the wound microenvironment when delivered using two different local application methods. Materials and Methods: In this preclinical study, we established an excisional full-thickness skin defect model involving approximately 30% of the total body surface area (TBSA). Five experimental groups were formed, each containing equal numbers of male and female rats: (1) subdermal ADSC injection (ADSC-I) (n = 8), (2) application of an acellular dermal matrix (ADM) seeded with ADSCs (n = 8) (ADSC-ADM), (3) ADM alone (n = 8), (4) subdermal saline injection (n = 8) (SS-I), and (5) an untreated skin-defect sham group (n = 8). Wound healing and wound microenvironment parameters were assessed at regular intervals using macroscopic and microscopic evaluations, as well as various quantitative measurements. The study was terminated when complete wound closure was achieved in all animals of at least one experimental group. Results: The most favorable healing outcomes were observed in the two ADSC-treated groups. More favorable microenvironmental conditions in the stem cell groups were detected from day 14 onward. Complete closure of the dermal defects occurred by day 32 in the ADSC-I group, whereas none of the other groups achieved full wound closure within the study period. Conclusions: Local application of adipose-derived stem cells may accelerate wound healing by favorably modulating the wound microenvironment.<\/jats:p>","DOI":"10.3390\/biom16020320","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T15:28:18Z","timestamp":1771428498000},"page":"320","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Local ADSC Delivery Methods Accelerate Healing of Large Unburned Full-Thickness Skin Defects by Promoting an Optimal Wound Microenvironment"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9737-859X","authenticated-orcid":false,"given":"Semra","family":"G\u00fcr\u00fcnl\u00fco\u011flu","sequence":"first","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Inonu University, Malatya 44280, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2538-5774","authenticated-orcid":false,"given":"Basri","family":"Sat\u0131lm\u0131\u015f","sequence":"additional","affiliation":[{"name":"Department of Liver Transplantation Institute, Faculty of Medicine, Inonu University, Malatya 44280, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1374-0783","authenticated-orcid":false,"given":"Mehmet","family":"G\u00fcl","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Inonu University, Malatya 44280, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6509-2012","authenticated-orcid":false,"given":"Muhammed","family":"D\u00fcndar","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Inonu University, Malatya 44280, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8315-1765","authenticated-orcid":false,"given":"Kubilay","family":"G\u00fcr\u00fcnl\u00fco\u011flu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Faculty of Medicine, Inonu University, Malatya 44280, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1865-4937","authenticated-orcid":false,"given":"Ezgi","family":"Karaaslan","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Inonu University, Malatya 44280, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3484-2137","authenticated-orcid":false,"given":"Ahmet","family":"Ko\u00e7","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Inonu University, Malatya 44280, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5710-6592","authenticated-orcid":false,"given":"Mehmet","family":"Aslan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Division of Emergency, Faculty of Medicine, Inonu University, Malatya 44280, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8044-0297","authenticated-orcid":false,"given":"Sezai","family":"Y\u0131lmaz","sequence":"additional","affiliation":[{"name":"Department of Liver Transplantation Institute, Faculty of Medicine, Inonu University, Malatya 44280, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4022-1276","authenticated-orcid":false,"given":"Mehmet","family":"Demircan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Faculty of Medicine, Inonu University, Malatya 44280, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9132-6115","authenticated-orcid":false,"given":"Tevfik Tolga","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Department of Liver Transplantation Institute, Faculty of Medicine, Inonu University, Malatya 44280, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/s41574-025-01107-x","article-title":"Neuro-immuno-endocrinology of the skin: How the environment regulates body homeostasis","volume":"21","author":"Slominski","year":"2025","journal-title":"Nat. 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