Affiliation: | 1. Department of Biomaterials School and Hospital of Stomatology Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, 250012 China Shenzhen Research Institute of Shandong University, Shenzhen, 518057 China;2. Department of Biomaterials School and Hospital of Stomatology Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, 250012 China;3. State Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong, 250100 China |
Abstract: | Treating bacterial biofilm infections on implanted materials remains challenging in clinical practice, as bacteria can be resistant by weakening the host defense from immune cells like macrophages. Herein, a metal-piezoelectric hetero-nanostructure with mechanical energy-driven antimicrobial property is in situ constructed on the Ti implant. Under ultrasonic irradiation, the formed piezotronic Ti (piezoTi) can promote the generation of reactive oxygen species (ROS) by facilitating local charge transfer at the surface, thus leading to piezodynamic killing of Staphylococcus aureus (S. aureus) while downregulating biofilm-forming genes. In addition, the stimulated macrophages on piezoTi display potent phagocytosis and anti-bacterial activity through the activation of PI3K-AKT and MAPK pathway. As a demonstration, one-time ultrasound irradiation of piezoTi pillar implanted in an osteomyelitis model efficiently eliminates the S. aureus biofilm infection and rescues the implant with enhanced osteointegration. By the synergistic effect of ultrasound-driven piezodynamic therapy and immuno-regulation, the proposed piezoelectric nanostructured surface can endow Ti implants with highly efficient antibacterial performance in an antibiotic-free, noninvasive, and on-demand manner. |