Antimicrobial hydrogel loaded with broccoli exosomes promotes anti-scarring healing of MRSA-infected wounds

Abstract

The treatment of methicillin-resistant staphylococcus aureus (MRSA)-infected wounds is severely challenged by antibiotic resistance and persistent inflammation. In this study, a photocrosslinked composite hydrogel material (SK@E-Au@Exos) was designed using silk protein methacryloyl hydrogel (SK) as a carrier loaded with broccoli-derived exosomes (Bro-Exos) and epigallocatechin gallate-gold nanoparticles (E-Au NPs). The material promoted scarless wound repair through synergistic anti-infection combined with immune regeneration modulation. In vitro experiments showed that SK@E-Au@Exos has excellent biocompatibility and can rapidly kill MRSA and E.coli, remove Reactive Oxygen Species (ROS), inhibit inflammation, and promote cell proliferation, migration, and vascularization. Importantly, SK@E-Au@Exos can regulate the immune regenerative microenvironment by inhibiting the Nuclear Factor kappa B (NF-kB) pathway and driving the macrophage to an anti-inflammatory phenotype. In a mouse MRSA-infected wound model, SK@E-Au@Exos resisted infection, scavenged ROS, inhibited inflammation, and promoted collagen ordering and neovascularization, ultimately realizing scarless healing of the infected wound. This study demonstrated the ability of SK@E-Au@Exos to promote the temporal regulation of “antibacterial-anti-inflammatory-regenerative” in wounds and revealed the molecular mechanism of SK@E-Au@Exos in regulating the immune microenvironment through key signaling pathways. In summary, SK@E-Au@Exos effectively promotes anti-infection and anti-scar healing of wounds infected with multidrug-resistant bacteria through its photothermal sterilization effect and exosome-controlled release of anti-inflammatory and repair-promoting substances. This provides an innovative strategy for the clinical treatment of wounds infected with drug-resistant bacteria, combining antibacterial and regenerative functions.