Atomic-to-Nanoscale Engineering of Piezocatalytic Heterojunctions for Ultrasound-Triggered Osteomyelitis Therapy

Osteomyelitis, primarily caused by methicillin-resistant Staphylococcus aureus (MRSA), poses critical clinical challenges, including drug-resistant infections and insufficient bone regeneration. Herein, we propose a mechano-electro-chemical energy conversion paradigm based on an atomic-to-nanoscale synergistic strategy, realized by constructing a heterojunction between sulfur-doped zinc oxide and bismuth ferrite (S-ZnO/BiFeO₃). At the atomic level, sulfur doping induces lattice distortion and oxygen vacancies, narrowing the bandgap of ZnO. At the nanoscale level, sulfur doping modulates crystal growth, transforming ZnO nanoblocks into thinner nanosheets that establish intimate interfacial coupling with BiFeO₃. This dual-scale synergy amplifies the piezoelectric coefficient (d₃₃) tenfold, significantly enhancing the ultrasound (US)-responsive piezocatalytic output. Under US, the enhanced piezocatalytic field facilitates directional charge migration and continuous reactive oxygen species (ROS) generation, achieving a 99.45% antibacterial rate against MRSA while effectively inhibiting biofilm growth. Transcriptomic profiling reveals that this energy conversion process eliminates MRSA via a multi-target collapse of membrane defense, ion homeostasis, and energy metabolism. Concurrently, S-ZnO/BiFeO₃ promotes osteogenic differentiation through US-triggered microcurrents and Zn²⁺ release. In vivo results validated robust bactericidal potency, osseointegrative kinetics, and excellent biocompatibility. This study establishes a mechano-electro-chemical energy conversion paradigm via atomic-to-nanoscale engineering, offering a high-performance platform for precise piezocatalytic therapy.