{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T10:13:09Z","timestamp":1788603189095,"version":"build-2803163510"},"reference-count":43,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The age-related decline in tissue regenerative capacity drives demand for interventions restoring physiological repair mechanisms. Glycyl-L-histidyl-L-lysine\u2013copper (GHK\u2013Cu) has demonstrated significant regenerative, anti-inflammatory, and antioxidant properties in preclinical models, prompting its increasing integration into aesthetic practice despite a paucity of standardized clinical guidelines. This systematic review evaluates the efficacy, safety, and regenerative mechanisms of GHK\u2013Cu in aesthetic medicine to clarify its clinical utility and inform future research. A systematic search of PubMed, Embase, and Cochrane CENTRAL was conducted from database inception through March 2026, following PRISMA guidelines. Eligible studies included clinical and preclinical models investigating GHK\u2013Cu as a standalone intervention for aesthetic applications. Twenty studies (18 preclinical; 2 randomized controlled trials) were included. Preclinical data consistently demonstrated that GHK\u2013Cu enhances extracellular matrix synthesis (type I collagen and glycosaminoglycans), modulates metalloproteinase activity, and promotes angiogenesis and cellular proliferation. It also exhibited significant anti-inflammatory effects by suppressing transforming growth factor-beta and interleukin-6. Clinically, GHK\u2013Cu improved patient-reported satisfaction after laser resurfacing and significantly reduced wrinkle volume and depth compared with controls. Additionally, advanced delivery systems, including microneedles and liposomes, markedly improved its transdermal bioavailability and efficacy. GHK\u2013Cu demonstrates a reasonable biological basis for use as a regenerative agent in aesthetic medicine, supported by available preclinical data. Nevertheless, the findings reported across studies were constrained by methodological variability and a limited number of well-designed clinical trials. Future research incorporating larger, controlled trials with standardized formulations, dosing regimens, and delivery methods will be necessary to close the translational gap and inform the development of consistent therapeutic protocols in clinical practice.<\/jats:p>\n                  <jats:p>Level of Evidence: 3 (Therapeutic)<\/jats:p>\n                  <jats:p>For image description, please refer to the figure legend and surrounding text.<\/jats:p>","DOI":"10.1093\/asj\/sjag169","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:53:27Z","timestamp":1787140407000},"source":"Crossref","is-referenced-by-count":0,"title":["The Regenerative Potential of Glycyl-\n                    <scp>L-<\/scp>\n                    Histidyl-\n                    <scp>L-<\/scp>\n                    Lysine\u2013Copperin Aesthetic Medicine"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8786-5246","authenticated-orcid":false,"given":"Jonathan","family":"Mokhtar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basel","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jewel","family":"Haddad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alma","family":"Said","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arya","family":"Menon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2954-0628","authenticated-orcid":false,"given":"Lucas","family":"Kreutz-Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna S","family":"Vyas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Curtis L","family":"Cetrulo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8191-8662","authenticated-orcid":false,"given":"Alexandre G","family":"Lellouch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"2026090505563983700_sjag169-B1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1089\/wound.2011.0356","article-title":"Characteristics of the aging skin","volume":"2","author":"Farage","year":"2013","journal-title":"Adv Wound Care (New Rochelle)"},{"key":"2026090505563983700_sjag169-B2","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1007\/s00268-003-7397-6","article-title":"Aging and wound 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