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<p>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-<i>L</i>-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. <i>In vitro</i> studies indicated that this MN system achieved effective killing of Methicillin-resistant <i>Staphylococcus aureus</i> (&gt;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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年7月25日

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  • Shuo Wang,
  • Jiaheng Liang,
  • Mengjie Sun,
  • Jin Chai,
  • Weihao Zhao,
  • Yibo Yan,
  • Peng Li

摘要

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.