Sulfur-regulated defect engineering for enhanced ultrasonic piezocatalytic therapy of bacteria-infected bone defects

Infection within bone defects remains an intractable issue in clinical practice, causing infectious bone destruction, disability, and death. Facing the deep-seated and refractory characteristics of the infection, an urgent request for rapid in situ sterilization and bone repair therapy is required. In this study, an ultrasound (US)-responsive sulfur-doped (SDBTO) barium titanate (BTO) piezocatalyst is constructed and the relationship between the amount of sulfur dopant and piezocatalysis performance, which is dominant for Staphylococcus aureus (S. aureus) elimination and bone regeneration, is explored. In addition to the band gap narrowing effect, an optimal sulfur doping introduces an appropriate amount of oxygen vacancies to BTO, which can increase the piezoelectric properties and improve the separation of electron-hole pairs, thus endowing SDBTO with outstanding piezocatalytic performance. SDBTO-1 presents superior antibacterial performance with 97.12% antibacterial efficiency against S. aureus. Simultaneously, SDBTO-1, activated by mild medical US, generates a moderate piezoelectric electric signal in vitro and boosts the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) by upregulating the TGF-β signaling pathway. SDBTO-1 successfully cures S. aureus-infected rat tibia bone defects with depressed inflammation and significantly improved bone regeneration. This work offers an effective ultrasonic piezocatalytic therapy through sulfur-regulated defect engineering.