{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:37:24Z","timestamp":1791578244518,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T00:00:00Z","timestamp":1711411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100002571","name":"American Association of Plastic Surgeons","doi-asserted-by":"publisher","award":["127358"],"award-info":[{"award-number":["127358"]}],"id":[{"id":"10.13039\/100002571","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2024,3,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hypertrophic scarring is a major source of morbidity. Sex hormones are not classically considered modulators of scarring. However, based on increased frequency of hypertrophic scarring in patients on testosterone, we hypothesized that androgenic steroids induce abnormal scarring and developed a preclinical porcine model to explore these effects. Mini\u2010swine underwent castration, received no testosterone (noT) or biweekly testosterone therapy (+T), and underwent excisional wounding. To create a delayed wound healing model, a subset of wounds were re\u2010excised at 2\u2009weeks. Scars from postoperative day 42 (POD42) and delayed wounds (POD28) were harvested 6\u2009weeks after initial wounding for analysis via histology, bulk RNA\u2010seq, and mechanical testing. Histologic analysis of scars from +T animals showed increased mean fibrosis area (16\u2009mm\n                    <jats:sup>2<\/jats:sup>\n                    noT, 28\u2009mm\n                    <jats:sup>2<\/jats:sup>\n                    +T;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.007) and thickness (0.246\u2009mm\n                    <jats:sup>2<\/jats:sup>\n                    noT, 0.406\u2009mm\n                    <jats:sup>2<\/jats:sup>\n                    +T;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.001) compared to noT. XX+T and XY+T scars had greater tensile burst strength (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.024 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.013, respectively) compared to noT swine.\u2009Color deconvolution analysis revealed greater deposition of type I and type III collagen as well as increased collagen type I:III ratio in +T scars. Dermatopathologist histology scoring showed that +T exposure was associated with worse overall scarring (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.05). Gene ontology analysis found that testosterone exposure was associated with upregulation of cellular metabolism and immune response gene sets, while testosterone upregulated pathways related to keratinization and laminin formation on pathway analysis. In conclusion, we developed a preclinical porcine model to study the effects of the sex hormone testosterone on scarring. Testosterone induces increased scar tissue deposition and appears to increase physical strength of scars via supraphysiologic deposition of collagen and other ECM factors. The increased burst strength seen in both XX and XY animals suggests that hormone administration has a strong influence on scar mechanical properties independent of chromosomal sex. Anti\u2010androgen topical therapies may be a promising future area of research.\n                  <\/jats:p>","DOI":"10.1096\/fj.202302144rrr","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T11:48:22Z","timestamp":1711453702000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Androgenic steroids induce pathologic scarring in a preclinical porcine model via dysfunctional extracellular matrix deposition"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0578-0011","authenticated-orcid":false,"given":"Erik","family":"Reiche","sequence":"first","affiliation":[{"name":"Division of Plastic Surgery Brigham and Women's Hospital \u2010 Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Plastic and Reconstructive Surgery Johns Hopkins University School of Medicine  Baltimore Maryland 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