{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T06:06:42Z","timestamp":1788934002389,"version":"build-2803163510"},"reference-count":79,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":7,"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"}],"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>Chronic wounds result from combined defects in vascular perfusion, inflammatory resolution, and epithelial repair. The skin's non\u2010neuronal cholinergic system (NNCS), formed by keratinocytes, endothelial cells, fibroblasts, and immune cells that synthesise and respond to acetylcholine (ACh), helps coordinate these processes through muscarinic and nicotinic receptors. Inhibition of acetylcholinesterase (AChE) increases local ACh concentrations and may engage two key pathways supported by preclinical data: M3 muscarinic receptor (M3 mAChR)\u2010endothelial nitric oxide synthase (eNOS)\u2010nitric oxide (NO)\u2010mediated vasodilation, and \u03b17 nicotinic acetylcholine receptor (\u03b17\u2010nAChR)\u2010mediated suppression of pro\u2010inflammatory cytokines. Donepezil is a reversible, selective AChE inhibitor with physicochemical properties compatible with dermal administration. Low\u2010dose or microneedle dermal delivery has produced dermal exposure with limited systemic uptake in animal and ex\u00a0vivo skin studies. In preclinical diabetic wound models, nicotinic receptor activation accelerated healing, reduced inflammatory signalling, and improved control of bacterial burden. We hypothesise that topical donepezil formulated for localised dermal delivery could restore cholinergic signalling within the wound microenvironment by increasing local ACh concentrations. This approach may complement metabolic therapies that support arginine\u2010NO coupling and redox balance. Controlled pilot studies should assess local cutaneous pharmacodynamics, perfusion responses, and wound\u2010closure outcomes.<\/jats:p>","DOI":"10.1111\/wrr.70211","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:21:03Z","timestamp":1788931263000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Topical Donepezil for Cholinergic Modulation in Chronic Wound Repair"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9317-4488","authenticated-orcid":false,"given":"Hui\u2010Qi","family":"Qu","sequence":"first","affiliation":[{"name":"The Center for Applied Genomics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlly","family":"Kao","sequence":"additional","affiliation":[{"name":"The Center for Applied Genomics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakon","family":"Hakonarson","sequence":"additional","affiliation":[{"name":"The Center for Applied Genomics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics The Perelman School of Medicine, University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Division of Pulmonary and Sleep Medicine Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Faculty of Medicine University of Iceland  Reykjavik Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"issue":"6","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1111\/j.1524-475X.2009.00543.x","article-title":"Human Skin Wounds: A Major and Snowballing Threat to Public Health and the Economy","volume":"17","author":"Sen C. 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