{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:54:52Z","timestamp":1790610892329,"version":"4.1.0"},"reference-count":89,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T00:00:00Z","timestamp":1779580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education","award":["NRF-2022R1I1A3069687"],"award-info":[{"award-number":["NRF-2022R1I1A3069687"]}]},{"award":["NRF-2022R1I1A3069687"],"award-info":[{"award-number":["NRF-2022R1I1A3069687"]}],"id":[{"id":"https:\/\/ror.org\/00b3tsf98","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Korean government","award":["2023R1A2C2004906"],"award-info":[{"award-number":["2023R1A2C2004906"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hypertrophic scars are characterized by excessive collagen deposition, fibrotic remodeling, and functional impairment. However, the ability of current models is limited in recapitulating human pathology. This study presents a novel approach using induced pluripotent stem cell-derived scar organoids to model hypertrophic scar characteristics in vitro. Following established protocols, human pluripotent stem cells were differentiated into skin organoids and induced fibrotic transformation by treatment with TGF-\u03b21 (10 ng\/mL) and hypoxia (5% O2) from day 45 onward. Scar organoids exhibited significant contraction and increased collagen I deposition compared with skin organoids. Immunofluorescence analysis showed reduced LHX2 expression, indicating loss of hair follicle development, while collagen I expression was significantly elevated. Dark-field imaging revealed marked morphological divergence between skin and scar organoids. RNA sequencing revealed distinct transcriptomic profiles. Expression of hair follicle-associated gene families (KRT and KRTAP) was upregulated in scar organoids, whereas epidermal structure-related genes (KRT4, KRT7, CLDN7, and WNT7) were downregulated. These findings demonstrate that iPSC-derived scar organoids successfully recapitulate key features of human hypertrophic scars, including excessive collagen production, loss of skin appendage development, and contractile behavior. This platform offers potential for future applications in drug screening, precision medicine, and understanding the molecular mechanisms underlying scar formation.<\/jats:p>","DOI":"10.3390\/cells15110969","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T10:19:52Z","timestamp":1779877192000},"page":"969","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Modeling Human Hypertrophic Scars with Induced Pluripotent Stem-Cell-Derived Scar Organoids Versus Skin Organoids"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0577-4836","authenticated-orcid":false,"given":"Hyun Mi","family":"Kim","sequence":"first","affiliation":[{"name":"BK21 FOUR KNU Convergence Educational Program of Biomedical Science for Creative Further Talents, Department of Medical Science, Kyungpook National University, Daegu 41944, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Jung","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5939-2550","authenticated-orcid":false,"given":"Suin","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4863-0508","authenticated-orcid":false,"given":"Se Ok","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7359-3044","authenticated-orcid":false,"given":"Ho Yun","family":"Chung","sequence":"additional","affiliation":[{"name":"BK21 FOUR KNU Convergence Educational Program of Biomedical Science for Creative Further Talents, Department of Medical Science, Kyungpook National University, Daegu 41944, Republic of Korea"},{"name":"Department of Plastic and Reconstructive Surgery, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,24]]},"reference":[{"key":"ref_1","first-page":"689","article-title":"The skin\u2019s barrier","volume":"144","author":"Jensen","year":"2009","journal-title":"G. 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