A Non‐Cryogenic Dugout‐Structured Microneedle Patch for Co‐Delivery of Irisin and Fibroblasts in Diabetic Wound Repair

ABSTRACT

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‐cell applications have been constrained by dehydration damage, cryogenic handling requirements, and complex fabrication processes. In this study, we developed a dugout‐structured microneedle patch (DSMNP) for non‐cryogenic co‐delivery of recombinant irisin and fibroblasts. Using a tri‐channel architecture together with a portable vacuum‐assisted loading method, the DSMNP achieved efficient loading of cell‐containing formulations without freeze‐thaw cycles or cryoprotectants. In vitro, payloads were distributed throughout the microchannels to a depth of approximately 900 µm, with fibroblasts released in a time‐dependent manner under cell‐compatible conditions. Irisin showed good cytocompatibility with fibroblasts, enhanced fibroblast migration, and modulated early NF‐κB and Akt signaling, evidenced by decreased p‐IκBα/p‐NF‐κB levels and increased Akt phosphorylation. In a streptozotocin (STZ)‐induced diabetic wound model, DSMNP‐mediated co‐delivery accelerated wound closure compared with topical application of the same payloads. Molecular and histological assessments revealed reduced TNF‐α expression, elevated fibronectin, TGF‐β1, and collagen deposition, and decreased α‐SMA levels. Together, these findings position the DSMNP as a practical, non‐cryogenic platform for delivering cells and bioactive proteins in diabetic wound healing.