Ti@ZnO Mediated Sonodynamic Disruption of Deep Implant Biofilms with Concomitant Immune Tracestream Remodeling

The bacterial biofilms (BF) formed by implant infection exhibit extremely strong antibiotic resistance, making implant infection a thorny secondary condition in orthopedics. This work presents a novel therapeutic strategy for preventing/combating biofilm infections by constructing ZnO nanostructures on Ti implants using the electrochemical deposition method, endowing the implants with deep sonodynamic therapeutic properties mediated by ultrasound. The strategy leverages the deep-penetrating properties of ultrasound to achieve dual therapeutic effects, generating bactericidal singlet oxygen in situ through the sonodynamic effect while simultaneously disrupting the immune barrier of biofilm against the host via ultrasonic cavitation. Systematic analysis in a murine implant infection model demonstrated efficient eradication of Staphylococcus aureus biofilms by this treatment. Crucially, beyond the direct bactericidal biofilm elimination, this approach reactivates the host immune response suppressed by biofilm infections. Further spatiotemporal analysis revealed the collaborative recruitment and the visualized tracestream of macrophages and neutrophils within the infected microenvironment. This research not only provides a sonosensitized implant-mediated sonodynamic therapeutic solution for controlling deep-seated implant infections but also lays a foundation for understanding the underlying mechanisms of immune cell recruitment, activation, and tracestream within the anti-infection immune microenvironment.