Immunomodulation and biofilm disruption of piezoelectric materials in bone infection

Bone infection remains a persistent clinical challenge due to biofilm formation, antibiotic resistance, and impaired bone regeneration. This manuscript focuses on the application of piezoelectric biomaterials in the treatment of bone infection and systematically elucidates their ability to convert in vivo mechanical stimulation into localized electrical signals and, in catalytically active systems, promote reactive oxygen species generation, thereby enabling efficient bacterial eradication and biofilm disruption. We further synthesize recent evidence showing that piezoelectric stimulation can modulate the infection-associated immune microenvironment and support osteogenesis and angiogenesis. Rather than considering antibacterial, immunomodulatory, and regenerative effects as parallel functions, we integrate them into a stage-adaptive therapeutic framework in which early biofilm disruption, bacterial eradication, and antimicrobial immune activation are followed by oxidative-stress control, inflammation resolution, pro-reparative immune remodeling, angiogenesis, and osteogenesis. This pathophysiology-oriented perspective highlights the potential of piezoelectric materials to coordinate the sequential therapeutic requirements of infected bone repair. Finally, current challenges and future perspectives regarding material design optimization, mechanistic understanding, and clinical translation are discussed.