Eliminate drug-resistant bacterial infection and accelerate cutaneous wound repair by antimicrobial, angiogenic, and immunomodulating microneedles

Abstract

Bacterial infection inevitably disrupts wound repair processes, including the inflammatory response and angiogenesis, thus impairing healing. Emerging antibiotic resistance makes drug-resistant bacterial wound infection a serious challenge in clinical practice. The efficacy of conventional wound dressings for therapeutic delivery is constrained by the barrier effects of skin. Herein, we present a novel strategy using a dissolving microneedle (MN) system for transderamlly delivering ε-poly-L-lysine (EPL)/hyaluronic acid (HA) nanoparticles (EH NPs) to effectively eliminate drug-resistant bacteria infection and accelerate wound healing. The electrostatic co-assembled EH NPs improved the bioactivities of two ingredients due to enhanced cell phagocytosis, enabling combinational antimicrobial, angiogenic, and anti-inflammatory abilities. In vitro studies indicated that this MN system achieved effective killing of Methicillin-resistant Staphylococcus aureus (>99.9%), upregulating endogenous nitric oxide release and CD31 expression in human vascular endothelial cells, and promoting the polarization of macrophages from Ml to M2. In a drug-resistant bacteria-infected skin wound mouse model, this MN system effectively promoted granulation tissue formation and collagen deposition by enhancing angiogenesis and reducing the inflammatory response, thereby significantly accelerating wound healing.