Engineered Long-Acting Mild Hyperthermia Microneedle Patches for Personalized Therapy of Infected Diabetic Wounds

The clinical treatment of chronically infected wounds faces multiple challenges, including antibiotic resistance, imprecise thermal control, and frequent dressing changes that hinder healing. Herein, we developed a multifunctional mild hyperthermic microneedle patch (GPD-NAS@PDA MN) based on the reversible phase-transition characteristics of lower critical solution temperature (LCST) thermoresponsive polymers, enabling single-application administration and precise long-term temperature regulation. Under near-infrared irradiation (NIR), the backing layer can actively protect surrounding normal tissues while efficiently killing bacteria and eradicating biofilms, thereby reducing reliance on antimicrobial agents. The needle tip continuously releases the angiogenic drug deferoxamine mesylate (DFO) via a stable network structure, synergistically promoting angiogenesis and tissue repair through photothermal effects. Transcriptomic analysis reveals that this system can regulate pathways related to oxidative stress and metabolic networks. In vivo studies confirm that the wound healing rate of the GPD-NAS@PDA MN is as high as 93.55% on the 14th day after a single application, thereby avoiding secondary tissue damage. In summary, the multifunctional microneedle system integrates precise hyperthermia, potent antibacterial and anti-biofilm activity, and anti-inflammatory and pro-angiogenic functions, avoiding the complexity of multiple drug combinations and frequent dressing changes in traditional therapies and providing a promising personalized strategy for chronic wound management.