{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:16:41Z","timestamp":1788355001783,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["247506"],"award-info":[{"award-number":["247506"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Wound Repair Regeneration"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Impairment of cutaneous healing occurs in association with numerous comorbidities including diabetes, vascular insufficiency and immobility. Standard management of chronic wounds includes removal of necrotic tissue and infection management, but no biomarkers are used to guide appropriate debridement distance. We hypothesized that by understanding the spatial distribution of proteins associated with keratinocyte differentiation and activation, oxidative stress biomarkers, as well as accumulation of oxidative damage, debridement protocols could be refined. Human tissue was isolated from (1) routine debridement procedures or (2) endstage at limb amputation. In debridement samples, wound edge epithelium typically exhibited hyperproliferation with or without epibole, with endstage wounds exhibiting a much thinner epidermis. Cytokeratin 14 expression was increased throughout the suprabasal epidermis with cytokeratin 10 and filaggrin expression attenuated; endstage wounds displayed downregulation of both cytokeratin 10 and filaggrin further from the wound edge than observed in debridement tissue. Cytokeratin 6, 16 and 17 were expressed in the wound edge and adjacent uninjured epidermis in both debridement and endstage wounds, while cytokeratin 16 and 17 were expressed in the non\u2010involved interfollicular epidermis in endstage limbs. Both phospho\u2010nuclear factor kappa B and the antioxidant transcription factor phospho\u2010nuclear factor\u2010erythroid 2\u2010related factor 2 show increased nuclear localization in the keratinocytes of endstage compared to debrided wounds concomitant with increased oxidative damage to lipids, protein and DNA in the epidermis. Our observations demonstrate increased tissue damage in endstage wounds compared to debridement tissue, which provides a preliminary starting point for the future investigation of several potential biomarkers associated with wound chronicity in humans.<\/jats:p>","DOI":"10.1111\/wrr.70196","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:29:27Z","timestamp":1788352167000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of Phenotype, Oxidative Stress and Biomacromolecule Oxidation in Human Chronic Skin Wound Epidermis in Active Debridement Tissue Versus Endstage Wounds"],"prefix":"10.1111","volume":"34","author":[{"given":"Dylan","family":"Tinney","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Carmichael","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Punkuj","family":"Chawla","sequence":"additional","affiliation":[{"name":"Chronic Wound and Lymphedema Clinic, St. Joseph's Healthcare: Parkwood Institute  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3658-2853","authenticated-orcid":false,"given":"David","family":"Keast","sequence":"additional","affiliation":[{"name":"Chronic Wound and Lymphedema Clinic, St. Joseph's Healthcare: Parkwood Institute  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9798-5197","authenticated-orcid":false,"given":"Douglas W.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry Western University  London Ontario Canada"},{"name":"Dentistry, Schulich School of Medicine and Dentistry Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"issue":"2","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/wrr.12994","article-title":"Chronic Wounds: Treatment Consensus","volume":"30","author":"Eriksson E.","year":"2022","journal-title":"Wound Repair and Regeneration"},{"issue":"1","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","DOI":"10.1111\/iwj.14522","article-title":"International Opinion\u2010The True Cost of Wounds for Canadians","volume":"21","author":"Queen D.","year":"2024","journal-title":"International Wound Journal"},{"issue":"9","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1177\/21621918251359554","article-title":"Human Wound and Its Burden: Updated 2025 Compendium of Estimates","volume":"14","author":"Sen C. 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