Spatiotemporally Controlled Antibacterial Therapy via Ultrasound‐Activated AIEgens Modulates the Immune Microenvironment to Promote Infected Bone Regeneration

The treatment of infected bone defects (IBD) has long been confronted with the dual challenges of inefficient bacterial eradication and impaired bone healing. Sonodynamic therapy (SDT) leverages the deep tissue penetration of ultrasound to activate sonosensitizers for the generation of reactive oxygen species (ROS), thereby enabling effective bacterial killing and biofilm disruption. However, conventional sonosensitizers are often limited by low ROS yields and persistent local inflammation that suppresses osteogenesis. In this study, we developed a cationic aggregation-induced emission luminogen, triphenylamine-thiophene-pyridinium salt (TTCNPy), for SDT-based treatment of IBD. Upon ultrasound activation, TTCNPy nanoparticles (TTCNPy NPs) efficiently generate ROS and selectively disrupt bacterial membrane structures, achieving pronounced antibacterial efficacy while maintaining good biosafety toward normal cells. In a Staphylococcus aureus-infected rat IBD model, TTCNPy+US treatment not only achieved effective in vivo bacterial clearance but also elicited an early innate immune response, markedly suppressing excessive inflammation and thereby accelerating bone repair. This work presents an ultrasound-activated sonodynamic antibacterial strategy that modulates the infectious microenvironment to promote bone regeneration, offering a promising avenue for the clinical translation of TTCNPy NPs in the management of IBD.