Multifunctional Janus hydrogel targeting mitochondrial regulation and inflammatory pathways promotes infected burn wound repair

Abstract

Infected burn wound repair is hindered by bacterial infection, inflammatory imbalance, and oxidative stress. Conventional antibiotic treatments face challenges from drug-resistant bacteria and biofilm formation, limiting their ability to improve the wound microenvironment. To address this change and provide a more comprehensive solution, we developed a Janus-structured smart hydrogel (P//GH + Ni + ZnO) that integrates NiCo₂O₄ nano-enzymes and ZnO nanoparticles. The combination of these two components provides synergistic antimicrobial, immunomodulatory, and mitochondrial protective effects, enhancing the therapeutic effect. In vitro, the hydrogel effectively inhibited drug-resistant bacteria, reduced ROS levels, stabilized mitochondrial membrane potential, and protected cellular function via PINK1/Parkin-mediated mitochondrial autophagy. Additionally, it promoted cell migration, angiogenesis, and tissue regeneration by optimizing the wound microenvironment. Building on the positive in vitro results, in vivo studies further confirmed its ability to accelerate wound healing, enhance M2 macrophage polarization, reduce TNF-α expression, and promote angiogenesis and tissue repair through TNF and VEGF signaling pathways. In summary, this Janus hydrogel significantly improved infected burn wound healing through its intelligent antimicrobial, immunoregulatory, and mitochondrial protective effects, offering a promising biomaterial solution for complex wound management and advancing the application of smart hydrogels in tissue repair.