Ultrasound-stimulated BTO-BSA-gen inhibits implant-associated infections by suppressing bacterial adhesion and potentiating aminoglycosides

Biofilms render implant-associated infections (IAIs) particularly challenging to manage. Inhibiting bacterial adhesion, the initial stage of biofilm formation, holds great potential in alleviating IAIs. In this work, we proved that the ultrasound(US)-generated electricity provided by barium titanate nanoparticles (BTO) could inhibit bacterial adhesion. Transcriptomics and metabolomics results validated that the BTO under ultrasound reduces the amount of integral membrane molecules in S. aureus and suppresses the expression of toxin molecules. Moreover, ultrasound-generated electricity provided by BTO improved the effectiveness of aminoglycosides through "bioelectric effect". Based on these findings, we further synthesized gentamicin(gen) loaded BTO-BSA (BTO-BSA-Gen), which demonstrated promising bactericidal effects in an ex vivo human skin model. Animal studies show the engineered BTO-BSA-Gen could substantially safeguard implants against bacteremia, consequently diminishing the onset and severity of IAIs. The frequency of hematogenous IAIs decreased significantly from 83.7% to 25% in response to ultrasound following BTO-BSA-Gen administration. This research offers valuable insights for the development of noninvasive, wireless therapies for IAIs treatment.