LIPUS-responsive meropenem-loaded nanobubbles enable biofilm disruption and bone repair in orthopedic implant-associated infections

Orthopedic implant-associated infections (OII), often driven by biofilm formation, pose persistent challenges to infection control and bone healing. This study introduces a dual-action therapeutic strategy employing low-intensity pulsed ultrasound (LIPUS)-responsive meropenem-loaded nanobubbles (NBs@MER) to simultaneously eradicate Escherichia coli biofilms and promote bone repair. In vitro, LIPUS activation of NBs@MER exhibited robust cavitation effects, which disrupted biofilm structure, enhanced antibiotic penetration, and improved antimicrobial efficacy. Concurrently, LIPUS stimulation modulated the immune microenvironment by polarizing macrophages toward the reparative M2 phenotype and enhancing osteogenic differentiation of bone marrow mesenchymal stem cells. In vivo studies using a rat OII model confirmed the dual functionality of the system, demonstrating marked reductions in bacterial burden and inflammation, alongside enhanced bone mineral density and trabecular architecture around infected implants. Collectively, this integrated strategy offers a promising platform for addressing the dual challenge of infection clearance and bone repair in OII management.