Non-invasive ultrasonic debridement of implant biofilms via hydrogen-sulfide releasing peptide nanoemulsions

Abstract

Implant contamination by bacterial biofilms remains a significant healthcare burden, often necessitating revision surgeries due to biofilm-enabled antibiotic resistance. Physical debridement, in combination with chemical antiseptics, is a simple and effective therapeutic strategy, but requires highly invasive surgical procedures and risks secondary infection events. Herein, we report a non-invasive, nanoparticle-enabled ultrasonic debridement strategy that exerts synergistic physical and chemical antiseptic effects to rapidly and efficiently clear implant-associated biofilms in situ. This approach is realized through the development of hydrogen sulfide releasing peptide nanoemulsions that preferentially target bacterial biofilms and can be vaporized via diagnostic ultrasound to spatiotemporally clear methicillin-resistant Staphylococcus aureus (MRSA) infections. Biophysical studies elucidate the mechanistic basis for the platform's anti-biofilm activity, and in vitro, ex vivo and in vivo experiments confirm efficacy in the context of MRSA-infected titanium implants. By exploiting the portable, low cost and safe nature of low intensity diagnostic ultrasound, this non-invasive approach avoids the collateral tissue damage associated with current surgical and high intensity acoustic ablative modalities.