{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:05:13Z","timestamp":1792789513332,"version":"4.5.0"},"reference-count":40,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gachon University","award":["GCU-202502080001"],"award-info":[{"award-number":["GCU-202502080001"]}],"id":[{"id":"https:\/\/ror.org\/03ryywt80","id-type":"ROR","asserted-by":"crossref"}]},{"award":["GCU-202502080001"],"award-info":[{"award-number":["GCU-202502080001"]}],"id":[{"id":"https:\/\/ror.org\/03ryywt80","id-type":"ROR","asserted-by":"publisher"}]},{"name":"LIBON Inc.","award":["LIBON-2502-01"],"award-info":[{"award-number":["LIBON-2502-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Pathological hypoxia following cutaneous injury is a critical driver of wound chronicity and fibrotic remodeling. The nuclear receptor binding SET domain protein 2 (NSD2)\/lysine demethylase 2A (KDM2A)\u2013histone H3 lysine 36 dimethylation (H3K36me2) axis is a known regulator of hypoxia-induced epithelial-to-mesenchymal transition (EMT) in malignancy; however, its role in skin repair remains largely unexplored. We investigated whether poly-L-lactic acid (PLLA) could attenuate fibrotic remodeling by modulating the NSD2\/KDM2A\u2013H3K36me2 axis and examining angiogenic signaling. We used a murine 9 mm punch-wound model for in vivo assessment and HaCaT keratinocytes and human dermal fibroblasts (HDFs) exposed to 2% O2 as in vitro hypoxia models. PLLA was administered to evaluate its impact on angiogenic signaling, collagen architecture, and the NSD2\/KDM2A pathway. PLLA was associated with increased angiogenic markers and reduced expression of several hypoxia-associated epigenetic and fibrotic markers. In mice, PLLA increased vascular endothelial growth factor (VEGF)\/VEGF receptor 2 expression and blood vessel abundance. In addition, PLLA decreased NSD2 and H3K36me2 levels while increasing KDM2A levels. Histological analysis showed less dense collagen staining and a change in the collagen type I\/type III staining ratio, alongside a smaller photographically defined residual lesion area. Under controlled hypoxic conditions in vitro, PLLA suppressed EMT-related transcription factors, including Snail, Slug, and Twist, in keratinocytes and attenuated transforming growth factor-\u03b21\/phosphorylated mothers against decapentaplegic homolog 2\/3 signaling and \u03b1-smooth muscle actin expression in fibroblasts. These findings support further study of PLLA-associated changes in vascular, epithelial, and fibrotic markers during wound remodeling.<\/jats:p>","DOI":"10.3390\/ijms27198874","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:30:07Z","timestamp":1791221407000},"page":"8874","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Poly-L-Lactic Acid Attenuates Fibrotic Remodeling During Cutaneous Wound Healing"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7486-9137","authenticated-orcid":false,"given":"Kyung-A","family":"Byun","sequence":"first","affiliation":[{"name":"Department of Anatomy & Cell Biology, College of Medicine, Gachon University, Incheon 21936, Republic of Korea"},{"name":"Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea"},{"name":"LIBON Inc., Incheon 22006, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9068-5813","authenticated-orcid":false,"given":"Hyoung Moon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anatomy & Cell Biology, College of Medicine, Gachon University, Incheon 21936, Republic of Korea"},{"name":"Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea"},{"name":"Maylin Apgujeong Clinic, Seoul 06024, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Seyeon","family":"Oh","sequence":"additional","affiliation":[{"name":"Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea"},{"name":"LIBON Inc., Incheon 22006, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Ki Woong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Anatomy & Cell Biology, College of Medicine, Gachon University, Incheon 21936, Republic of Korea"},{"name":"Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea"},{"name":"Maylin Clinic Jamsil Lotte Hotel Branch, Seoul 05554, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Ji Min","family":"Lee","sequence":"additional","affiliation":[{"name":"Director Global Clinic Gangnam, Seoul 06611, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0595-5645","authenticated-orcid":false,"given":"Kuk Hui","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8678-8932","authenticated-orcid":false,"given":"Kyunghee","family":"Byun","sequence":"additional","affiliation":[{"name":"Department of Anatomy & Cell Biology, College of Medicine, Gachon University, Incheon 21936, Republic of Korea"},{"name":"LIBON Inc., Incheon 22006, Republic of Korea"},{"name":"Department of Health Sciences and Technology, Gachon Advanced Institute for Health & Sciences and Technology (GAIHST), Gachon University, Incheon 21999, Republic of 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