Ultrasound-responsive BTO@MSN-Cu/chitosan coatings on titanium implants with synergistic antibacterial and angiogenic effects

Sonodynamic therapy (SDT) is a promising strategy for treating implant-associated infections (IAIs), yet achieving concurrent antibacterial efficacy and tissue regeneration remains challenging. In this study, piezoelectric BaTiO₃ (BTO) nanoparticles were encapsulated within Cu-doped mesoporous silica (MSN) via a sol-gel method to construct core-shell BTO@MSN-Cu nanoparticles, which were subsequently electrophoretically co-deposited with chitosan onto titanium (Ti) substrates to form a multifunctional coating. Under ultrasound (US) irradiation, the BTO core generated reactive oxygen species (ROS) via piezocatalysis, while the MSN shell enabled controlled and stimulus-responsive release of Cu ions. Theoretical calculations revealed that the core-shell heterostructure enhances piezoelectric potential and charge separation. The resulting coating exhibited potent antibacterial efficiency (>99% against S. aureus, >95% against E. coli), while also supporting osteoblast adhesion and proliferation and enhancing endothelial cell migration and angiogenesis. Overall, this chitosan/BTO@MSN-Cu coating integrates US-activated sonodynamic action and Cu ion therapy to provide a dual-modal strategy for infection control and tissue repair in IAIs.