Eliminate Drug-Resistant Bacterial Infection and Accelerate Cutaneous Wound Repair by Antimicrobial, Angiogenic, and Immunomodulating Microneedles
Bacterial infection disrupts wound repair through sustained inflammatory responses and impaired angiogenesis, while antibiotic resistance severely limits conventional therapies. This study reports a dissolving microneedle (MN) system for transdermal delivery of ε-poly-L-lysine (EPL)/hyaluronic acid (HA) nanoparticles (EH NPs) to eliminate methicillin-resistant Staphylococcus aureus (MRSA) and accelerate wound healing. Electrostatic co-assembly of EPL and HA yields nanoparticles with enhanced cellular phagocytosis, enabling combined antimicrobial, angiogenic, and anti-inflammatory activities. In vitro, the MN system eradicates >99.9% of MRSA, upregulates endogenous nitric oxide release and CD31 expression in human vascular endothelial cells, and promotes macrophage polarization from M1 to M2 phenotype. In a drug-resistant bacteria-infected skin wound mouse model, the MN system significantly enhances granulation tissue formation and collagen deposition by promoting angiogenesis and reducing inflammation, thereby accelerating wound closure. This multifunctional microneedle platform addresses the limitations of conventional dressings by overcoming the skin barrier for efficient transdermal delivery of synergistic bioactive nanoparticles, offering a promising clinical strategy for infected wound management.