Ultrasound‐Controlled Electron‐Phonon Coupling Augmenting Catalysis of Piezoelectric‐Based Sonosensitizer Safely Against Osteomyelitis

Abstract The energy transfer way and efficiency of ultrasound (US) to piezoelectric materials in fluid determines the US catalytic performance of materials and the subsequent sono‐therapeutic effects for deep infection diseases. Herein, on insonation, the microbubble cavitation occurs near the surface of barium orthotitanate/berberine chloride nanoparticles (BTO/Ber NPs), often forming sonoluminescence and high pressure. The light further activates Ber, and the electron transfer happens between activated Ber and changing energy levels of BTO NPs caused by changing pressure. Meanwhile, ultrasound‐driven piezoelectric electron‐phonon coupling simultaneously narrows bandgap and prolongates carrier‐lifetime, leading to more ROS generation. Hence, BTO/Ber NPs show great antibacterial activity against Staphylococcus aureus (99.80 ± 0.09%) by microbubble‐mediated sonoporation and catalysis. Meanwhile, BTO/Ber NPs improve bone regeneration by decreasing the inflammatory response and enhancing osteoblast differentiation. US‐mediated microbubbles may offer a safe and efficient treatment to millions of patients suffering from osteomyelitis and pave the way for the highly safe use of ultrasound in deep infections.