Shikonin-functionalized magnetic nanoparticles mediated magnetothermodynamic therapy with synergistic antibacterial efficacy and immunomodulation for accelerated infected wound healing

Infected skin wounds healing remains a great clinical challenge due to the complexity of the wound healing process, involving infection control and subsequent immunomodulation. Magnetothermodynamic (MTD) therapy, combining the magnetothermal effect and thermal-amplified Fenton reactivity, is a promising strategy for combating bacterial infections. However, its therapeutic efficacy in wound healing is compromised due to its insufficient ability to address inflammation. Herein, we develop a multifunctional polyvinyl alcohol/gelatin composite hydrogel (MagSK hydrogel) incorporating shikonin-functionalized magnetic nanoparticles (MagSK NPs) to achieve microenvironment-responsive and programmed treatment of infected wounds. During infectious period, MagSK NPs mediated MTD effect can effectively eradicate bacteria and destroy dense biofilm. In subsequent tissue repair stage, MagSK hydrogel suppress excessive inflammation through scavenges reactive oxygen species (ROS), modulates macrophage polarization. Transcriptomic analysis further revealed that the treatment coordinately downregulates inflammatory pathways and upregulates genes critical for tissue proliferation and remodeling. Both in vitro and in vivo studies demonstrate that MagSK hydrogel effectively eliminates bacteria, mitigates inflammation, enhanced angiogenesis and markedly accelerated wound healing. Collectively, our findings highlight a novel strategy for infected wound healing via MagSK-mediated magnetothermodynamic therapy with synergistic antibacterial and immunomodulatory effects.