Ultrasound Activated Piezoelectric Catalysis and Neurogenic Activity for Effective Therapy of MRSA Infected Bone Defects by Phase/Defect‐Engineered Barium Strontium Titanate

Infected bone defects are a growing global health issue, with risks including bone destruction, disability, and even death. The main clinical challenge is the difficulty in simultaneously achieving effective antibacterial action and promoting bone regeneration. Calcination at 800°C induces a phase transition from cubic (C-BSTO) to polarized tetragonal (T-BSTO), imparting piezoelectric properties. Subsequent treatment with sodium borohydride generates oxygen vacancies, enhancing polarization and piezoelectric performance. The synthesized T-BSTO-V_o achieves 99.83% antibacterial efficiency against methicillin-resistant Staphylococcus aureus (MRSA) under 1.5 W cm² ultrasound (US) irradiation for 20 min. Mild US irradiation activates a piezoelectric signal, promoting Schwann cell (SC) neurogenic differentiation via PI3K-AKT signaling and intracellular Ca²⁺ elevation. Further studies showed that the synergy of the neurotransmitter of SCs and piezoelectric electric signal increased the osteogenic differentiation of human bone marrow mesenchymal stem cells (BMSCs). Consequently, US-irradiated T-BSTO-V_o effectively promotes the innervated bone regeneration in the MRSA-infected bone defect model through rapidly killing bacteria, modulating the immune microenvironment. This study offers a new approach for developing bioactive sonosensitizers through phase/defect engineering, and treats MRSA-infected bone defects through enhanced piezocatalytic effect and innervated bone regeneration.