{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:24:19Z","timestamp":1793298259092,"version":"4.5.0"},"reference-count":128,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Psoriasis, an inflammatory skin disease, affects nearly 43 million individuals globally, and patients are 59% more likely to have type 2 diabetes. In this study, tissue-engineered psoriatic human skin substitutes were produced using keratinocytes and fibroblasts derived from patients with plaque psoriasis, and were enriched with human T lymphocytes to amplify the inflammation. Tissue-engineered healthy human skin substitutes served as a control. The psoriatic model exhibited type 2 diabetes-like features, including diminished uptake of insulin and glucose, with glucose uptake being approximately eight times lower than in the healthy skin model. Insulin-like growth factor signalling was impaired with lower insulin-like growth factor 1 (IGF-1), and insulin-like growth factor binding protein 2 (IGFBP-2) levels, as well as elevated insulin-like growth factor binding protein 4 (IGFBP-4) levels in the cell culture supernatants. This is the first human skin model to concurrently exhibit both psoriatic inflammation and insulin resistance. Moreover, to assess therapeutic potential, phloretin-loaded microneedle patches were applied for 1 week. They reduced the levels of cytokines involved in both psoriasis and insulin resistance: granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage migration inhibitory factor (MIF), and interleukin-17A (IL-17A). This anti-inflammatory activity was more pronounced than that of systemic-like methotrexate and methotrexate-loaded microneedle patches. The microneedles loaded with phloretin tended to enhance insulin uptake and reduce IGFBP-4 levels in the supernatants; however, these changes were not statistically significant. Prolonging the treatment period beyond 1 week or combining it with another compound loaded into the microneedles that improves insulin sensitivity may increase the efficacy of this approach by simultaneously addressing psoriasis and type 2 diabetes.<\/jats:p>","DOI":"10.3389\/fmolb.2026.1830240","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:33:23Z","timestamp":1780979603000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A tissue-engineered human psoriatic skin model: targeting inflammation and glucose metabolism dysregulation in psoriasis using microneedle patches"],"prefix":"10.3389","volume":"13","author":[{"given":"Yasmine","family":"Ruel","sequence":"first","affiliation":[{"name":"Facult\u00e9 de Pharmacie, Universit\u00e9 Laval","place":["Qu\u00e9bec City, QC, Canada"]},{"name":"Centre de Recherche en Organog\u00e9n\u00e8se Exp\u00e9rimentale de l\u2019Universit\u00e9 Laval\/LOEX, Axe M\u00e9decine R\u00e9g\u00e9n\u00e9ratrice, Centre de Recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval","place":["Qu\u00e9bec City, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma","family":"Moawad","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie, Universit\u00e9 de Montr\u00e9al","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Cortez Ghio","sequence":"additional","affiliation":[{"name":"In Silico Data Science","place":["Qu\u00e9bec City, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Brambilla","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie, Universit\u00e9 de Montr\u00e9al","place":["Montreal, QC, Canada"]},{"name":"School of Pharmaceutical Sciences, University of Geneva","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxane","family":"Pouliot","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Pharmacie, Universit\u00e9 Laval","place":["Qu\u00e9bec City, QC, Canada"]},{"name":"Centre de Recherche en Organog\u00e9n\u00e8se Exp\u00e9rimentale de l\u2019Universit\u00e9 Laval\/LOEX, Axe M\u00e9decine R\u00e9g\u00e9n\u00e9ratrice, Centre de Recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval","place":["Qu\u00e9bec City, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.biopha.2018.02.103","article-title":"The potential pathogenic role of IL-17\/Th17 cells in both type 1 and type 2 diabetes mellitus","volume":"101","author":"Abdel-Moneim","year":"2018","journal-title":"Biomed. and Pharmacother."},{"key":"B2","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s40842-024-00202-8","article-title":"The impact of insulin resistance and glycaemic control on insulin-like growth factor-1 in patients with type 2 diabetes: a cross-sectional study","volume":"10","author":"AbdlWhab","year":"2024","journal-title":"Clin. 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