{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:25:04Z","timestamp":1787030704090,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Diabetic wounds remain difficult to treat due to persistent inflammation and impaired fibroblast function, which slow tissue repair. Microneedle systems provide a minimally invasive route for localized delivery, but live\u2010cell applications have been constrained by dehydration damage, cryogenic handling requirements, and complex fabrication processes. In this study, we developed a dugout\u2010structured microneedle patch (DSMNP) for non\u2010cryogenic co\u2010delivery of recombinant irisin and fibroblasts. Using a tri\u2010channel architecture together with a portable vacuum\u2010assisted loading method, the DSMNP achieved efficient loading of cell\u2010containing formulations without freeze\u2010thaw cycles or cryoprotectants. In vitro, payloads were distributed throughout the microchannels to a depth of approximately 900\u00a0\u00b5m, with fibroblasts released in a time\u2010dependent manner under cell\u2010compatible conditions. Irisin showed good cytocompatibility with fibroblasts, enhanced fibroblast migration, and modulated early NF\u2010\u03baB and Akt signaling, evidenced by decreased p\u2010I\u03baB\u03b1\/p\u2010NF\u2010\u03baB levels and increased Akt phosphorylation. In a\n                    <jats:italic>streptozotocin<\/jats:italic>\n                    (STZ)\u2010induced diabetic wound model, DSMNP\u2010mediated co\u2010delivery accelerated wound closure compared with topical application of the same payloads. Molecular and histological assessments revealed reduced TNF\u2010\u03b1 expression, elevated fibronectin, TGF\u2010\u03b21, and collagen deposition, and decreased \u03b1\u2010SMA levels. Together, these findings position the DSMNP as a practical, non\u2010cryogenic platform for delivering cells and bioactive proteins in diabetic wound healing.\n                  <\/jats:p>","DOI":"10.1002\/adhm.71598","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:24:17Z","timestamp":1787027057000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Non\u2010Cryogenic Dugout\u2010Structured Microneedle Patch for Co\u2010Delivery of Irisin and Fibroblasts in Diabetic Wound Repair"],"prefix":"10.1002","author":[{"given":"Yu\u2010Chi","family":"Pan","sequence":"first","affiliation":[{"name":"Graduate Institute of Medicine College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsi\u2010Chen","family":"Tung","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering National Cheng Kung University  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Tzu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Chang Gung Memorial Hospital  Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9170-6268","authenticated-orcid":false,"given":"Hung\u2010Pei","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery Department of Surgery Kaohsiung Medical University Hospital Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien\u2010Ju","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmacy College of Pharmacy Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu\u2010Hung","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medicine College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Division of Plastic Surgery Department of Surgery Kaohsiung Medical University Hospital  Kaohsiung Taiwan"},{"name":"Department of Surgery School of Medicine College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8438-6291","authenticated-orcid":false,"given":"Hung\u2010Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering National Cheng Kung University  Tainan Taiwan"},{"name":"Medical Device Innovation Center National Cheng Kung University  Tainan 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