Engineered Yeast-Derived Hyaluronic Acid Microneedles with Immunomodulatory and Synergistic Antibacterial Activities for Diabetic Wound Healing

Diabetic wounds represent one of the most serious chronic complications, marked by bacterial infection, persistent inflammation, and dysregulated macrophage polarization, all of which contribute to impaired healing and impose substantial clinical and economic burdens. Existing therapies are frequently constrained by inadequate drug penetration and repetitive administration requirements. To overcome these limitations, we engineered a dissolving microneedle (MN) patch composed of hyaluronic acid and collagen tripeptide for direct intradermal delivery of live <i>Saccharomyces cerevisiae</i> (<i>S. cerevisiae</i>). Leveraging the natural metabolic activity of <i>S. cerevisiae</i>, this MN system facilitates the sustained release of ethanol and β-glucan, providing simultaneous antibacterial and immunomodulatory benefits. In a diabetic mouse model with infected wounds, a single application of the <i>S. cerevisiae</i>-laden MNs markedly improved antibacterial outcomes and accelerated wound closure. These results underscore the potential of this biohybrid microneedle platform as a promising therapeutic strategy for the management of chronically infected wounds. Further advancement of this system may yield an effective treatment paradigm for diabetic wound therapy.