O₂-releasing microneedle platform eradicates drug-resistant bacterial biofilm via metabolic interference and innate immune reactivation.

Abstract

Biofilm-associated infections pose formidable clinical challenges due to their complicated microenvironment characterized by dense extracellular polymeric substances (EPS), hypoxia, and excessive H₂O₂. While microneedles can mechanically penetrate biofilms, their efficacy is limited by poor diffusion of antibacterial agents through EPS and secondary infection resulting from escaping planktonic bacteria. Herein, we proposed an oxygen-powered microneedle (FeCN@MN) that synergistically eradicates biofilms through a dual mechanism: ferroptosis-like death-mediated bacterial killing and neutrophil reactivation. The microneedle utilizes sodium percarbonate (SPO) particles that react with interstitial fluid to generate O₂ bubbles, which propel the loaded FeS₂-decorated carbon nanospheres (FeCN) to disperse throughout biofilms. Moreover, the FeCN@MN can reactivate neutrophils to scavenge planktonic bacteria escaping from biofilm disintegration through enhanced chemotaxis and respiratory burst, further inhibiting potential recurrence of infection. In vitro experiment reveals that iron overload disrupts amino acid metabolism and peroxide accumulation, promoting bacterial ferroptosis-like death. Furthermore, neutrophil functional tests show enhanced chemotaxis and killing ability to MRSA bacteria. In MRSA biofilm-infected diabetic wound model, FeCN@MN significantly dismantles biofilms, and effectively eliminates infections. In conclusion, this two-stage therapeutic approach combining bacterial metabolic interference with immune response reactivation provides a promising strategy in eradicating drug-resistant bacterial biofilm-associated infections.