Ultrasound activated Zn Ga layered double oxide as ROS antimicrobial-healing system boosts antimicrobial effect and infected bone regeneration

Bone infections are destructive diseases caused by microbial seeding, and sonodynamic therapy (SDT) can efficiently eliminate bacteria in deep bone tissue by generating reactive oxygen species (ROS). This study presents a novel ROS antimicrobial-healing system (ZG PEG with Zn and Ga as layered double oxide) for treating bone infections. SDT effectively eradicates biofilms and disrupts bacterial cell membranes. Transcriptome analysis shows that ZG PEG + US influenced the antioxidant system, metabolic processes and biofilm formation in methicillin-resistant Staphylococcus aureus (MRSA). Additionally, the regulation of the infected immune microenvironment creates a conducive environment for osteogenic differentiation. Low ROS concentrations promote bone repair, and gallium inhibits osteoclastogenesis directly. The triple actions of rapid bactericidal effect, osteoclastogenesis inhibition, and bone regeneration establish a spatiotemporal functional cascade in the ROS antimicrobial-healing system. • The demonstration of the sonosensitizer broad-spectrum antimicrobial activity against pathogens such as MRSA and P. aeruginosa . • Insights into the molecular mechanisms underpinning these effects, as revealed by RNA sequencing analysis of the treated specimens. • This study pioneered the classification of US intensity, and demonstrated that low-intensity US triggers low ROS concentrations to promote bone repair.