Defective S-TiO2−x/CeO2 Heterojunction for Mutual Reinforcing Chemodynamic/Sonocatalytic Antibacterial Therapy and Sonoelectric/Ion-Activated Bone Regeneration

Abstract

Sonocatalysis and chemodynamics have attracted widespread attention in antibacterial therapy. The transfer efficiency of electrons plays an important role in sonocatalysis and chemodynamics, and how to regulate electron transfer and achieve mutual-reinforcement between sonocatalysis and chemodynamic to achieve efficient antibacterial therapy is a difficult problem. Here, this study develops a defective S-doped TiO₂ and CeO₂ heterojunction(S-TiO_2−x/CeO₂）sonosensitizer that can enhance chemodynamic therapy by regulating valence transitions of Ce^III/Ce^IV by sonoelectrons, and enhancing sonocatalytic therapy by creating heterojunctions to accelerate the transfer of interface electron, thereby achieving mutual reinforcement of sonocatalysis and chemodynamic. It could kill 99.3% of S. aureus under ultrasound (US) irradiation . Due to the presence of mixed valence states Ce^III/Ce^IV in CeO₂, S-TiO_2−x/CeO₂ could be as oxy-substrates. Ce⁴⁺ can deplete glutathione and reacts with H₂O₂ in bacteria to produce reactive oxygen species (ROS). These activities combines with ROS generated from sonocatalysis, resulting in bacterial death. Meanwhile, the electrical signal generated by S-TiO_2−x/CeO₂ under US stimulation and the cerium ions could activate the Wnt/β-catenin signaling pathway to induce hBMSCs to differentiate into osteoblast. S-TiO_2−x/CeO₂ successfully treats osteomyelitis under US irradiation by effectively clearing infection, suppressing inflammatory, and promoting bone regeneration, and it provides effective treatment for patients with deep infection.