An Infection-Responsive KCoF3@Fe-HA Hydrogel for Localized Co/Fe Dual Fenton-like Therapy of MRSA-Infected Wounds

Methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds remain difficult to treat because bacterial persistence, inflammation, antimicrobial resistance, and poorly controlled local toxicity can jointly impair tissue repair. Herein, we report an infection-responsive KCoF3@Fe-HA hydrogel that integrates potassium cobalt fluoride (KCoF3) with an Fe3+-crosslinked hyaluronic acid (HA) network for localized Co/Fe dual Fenton-like antibacterial therapy. Notably, the use of KCoF3 in antibacterial wound dressing systems has not yet been reported. In this design, KCoF3 serves as a confined Co reservoir, while the Fe-HA network provides catalytic Fe species and a biodegradable hydrogel matrix. The introduction of Co-mediated Fenton-like activity may broaden the effective catalytic pH range and compensate for the limited activity of Fe-based Fenton-like systems under infection-relevant weakly acidic conditions. Meanwhile, the HA network provides infection responsiveness, allowing weak acidity and bacteria-associated hyaluronidase to promote localized network relaxation and degradation. Together with the reservoir-like KCoF3 structure, this design enables sustained Fe/Co release around infected tissues, helping to maintain local antibacterial activity while reducing burst Co exposure and unnecessary metal leakage. KCoF3@Fe-HA showed stronger Fenton-like catalytic activity than single-metal hydrogel systems. The hydrogel exhibited broad-spectrum antibacterial activity against MRSA, Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli) and effectively reduced bacterial burden in an MRSA-infected full-thickness wound model. Wounds treated with KCoF3@Fe-HA closed faster and showed weaker inflammatory signals, greater collagen deposition, and increased angiogenesis. Cytocompatibility, hemolysis, blood analysis, and major-organ histology supported its preliminary biosafety. This work provides a localized Co/Fe Fenton-like dressing strategy for antibiotic-free MRSA-infected wound healing, presenting KCoF3 as a confined Co reservoir integrated with an infection-responsive HA hydrogel network.