Piezoelectric Nanostructured Surface for Ultrasound‐Driven Immunoregulation to Rescue Titanium Implant Infection

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.