Specific Activation of the STING Pathway by Engineering Piezoelectric Hydrogel Microspheres for Boosting Implant Infection Immunotherapy

Abstract

Implant-associated infections (IAIs) represent the primary cause of prosthetic implant failure. Bacterial biofilms hinder the host’s immune response, creating ″immune cold zones.″ ″Immune activation therapy″ presents a viable strategy for addressing IAIs. Nonetheless, focusing solely on regulating innate immune cells like macrophages falls short for effective antibiofilm outcomes. Herein, a multifunctional antimicrobial system capable of utilizing ultrasound (US)-induced tandem catalysis and activating innate and adaptive antimicrobial immune responses is proposed. The integration of piezoelectric barium titanate with STING plasmids both encapsulated in liposomes and embedded in hydrogel microspheres. US activation generates reactive oxygen species, effectively destroying biofilms and subsequently exposing bacterial antigens. US can destroy liposomes and release STING plasmids, thereby activating the cGAS-STING pathway and triggering antimicrobial innate immunity. Additionally, it can also induce DC maturation, enhance bacterial antigen presentation, alleviate immunosuppression, and boost adaptive immunity. This study proposes a promising strategy combining antimicrobial and immunotherapy, offering an alternative to antibiotics for IAI treatment.