Ultrasound-mediated ion-piezoelectric remodeling of the infected implant microenvironment for biofilm eradication and antibacterial immunity

Background Implant-associated infections (IAIs) remain major clinical challenges because bacterial biofilms form a protected implant microenvironment that limits antibiotic penetration, reduces immune recognition, and promotes infection recurrence. Although current antibacterial strategies can reduce bacterial viability, they often fail to coordinately disrupt biofilm architecture, collapse bacterial metabolic fitness, and restore host antibacterial immunity. Technology In this study, we propose an ultrasound (US)-mediated ion-piezoelectric infection microenvironment remodeling technology for the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-associated implant infections. First, CuS/MoS 2 heterojunctions were constructed through sulfidation/in situ assembly. Under US stimulation, MoS 2 generates piezoelectric polarization, while the CuS/MoS 2 heterointerface promotes charge separation and enhances the piezocatalytic generation of reactive oxygen species (ROS). Meanwhile, CuS undergoes pH/US-responsive Cu 2+ release within the infection-associated acidic environment and under US disturbance. By integrating US-triggered piezo-oxidative damage with Cu 2+ -mediated ionic metabolic interference, this technology remodels the infected implant microenvironment through biofilm structural disruption, bacterial metabolic imbalance, and host antibacterial immune activation. Results The US-mediated ion-piezoelectric remodeling strategy effectively dismantled MRSA biofilms rich in extracellular polymeric substances (EPS), damaged bacterial membranes, and induced metabolic dysfunction characterized by impaired iron–sulfur (Fe–S) cluster-dependent metabolism, ATP depletion, and NAD + /NADH imbalance. Beyond direct antibacterial activity, this strategy increased the immune visibility of disrupted biofilms, enhanced macrophage-mediated bacterial clearance, and was associated with enhanced DC maturation and STING-related innate immune signaling. In a murine IAI model, US-activated treatment reduced implant bacterial burden, disrupted residual surface biofilms, and shifted the local immune microenvironment toward antibacterial activation. Rechallenge experiments further showed strengthened antibacterial immune memory and improved protection against secondary MRSA biofilm exposure. Overall, this work establishes US-mediated ion-piezoelectric remodeling as a localized antibacterial strategy that coordinates biofilm disruption, bacterial metabolic interference, and host antibacterial immunity for implant-associated infection management.