Leveraging piezo-augmented copper-induced bacterial death of sub-1 nm CuO-SrTiO3-x heterojunction nanosheets for osteomyelitis eradication

Osteomyelitis is a refractory bacterial infection of bone, presenting significant clinical management challenges due to its limited therapeutic outcome. Here, we developed heterojunction-structured sub-1 nm copper oxide-decorated strontium titanate nanosheets (Cu-STO NSs), which integrate piezocatalytic reactive oxygen species (ROS) generation with augmented copper-induced bacterial death for synergistic osteomyelitis treatment. Under ultrasound (US) irradiation, the oxygen vacancies and heterojunction structure of Cu-STO NSs facilitate the separation of piezo-generated electron–hole pairs while reducing energy barriers, thereby enhancing ROS generation. This process is augmented by the US-accelerated Cu 2+ /Cu + redox cycling, which enables sustained hydroxyl radicals supply via Fenton-like reactions. The US-driven piezocatalytic action simultaneously enhances bacterial membrane permeability, facilitating intracellular copper overload and thereby triggering copper-induced metabolic toxicity in Staphylococcus aureus ( S. aureus ). Subsequent release of bioactive Cu and Sr ions from Cu-STO NSs significantly upregulates osteogenic differentiation of bone marrow stromal cells. In rat osteomyelitis, Cu-STO NSs achieve efficient bacterial eradication while stimulating on-demand bone regeneration. This work thus presents a non-invasive, spatiotemporal controlled copper-induced bacterial death strategy that concurrently addresses antibacterial and osteogenic challenges in infected bone regeneration.