Harnessing Acoustic Energy Against Orthopedic Biofilms: Ultrasound-Based Therapeutic Strategies for Implant-Associated and Bone Infections.

Abstract

Orthopedic implant-associated and bone infections remain difficult to eradicate because microorganisms can establish biofilms on prosthetic surfaces, devitalized bone, and synovial aggregates. These communities impede antimicrobial penetration and host clearance, while metabolically altered and persister-like states further contribute to treatment failure and recurrence. Ultrasound-based technologies are being investigated as adjunctive strategies because acoustic energy can provide mechanical biofilm disruption, trigger local drug release, activate sonosensitizers, enhance catalytic reactions, and, in selected systems, modulate the infected tissue microenvironment. This narrative review critically examines the mechanistic basis and translational evidence for ultrasound-assisted antimicrobial delivery, phase-transition systems, sonodynamic therapy (SDT), ultrasound-enhanced nanozyme catalysis, piezocatalytic strategies, and multifunctional hydrogel platforms in orthopedic infection. Particular attention is given to the maturity and clinical relevance of the infection models, the contribution of non-ultrasound co-therapies, ultrasound dose reporting, and the distinction between direct regenerative effects and secondary recovery after bacterial clearance. Current evidence remains predominantly preclinical and heterogeneous, and clinical translation will require standardized acoustic dosimetry, chronic and polymicrobial infection models, tissue-specific safety assessment, and integration with established surgical and antimicrobial pathways.