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

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.