Engineered Nature‐Based Sonosensitizer for Broad‐Spectrum Infectious Tissue Repair via Sono‐Ionic Therapy

Repairing infectious tissues, particularly bone and wound infections, poses significant challenges to clinicians due to the lack of effective treatment modalities. Sonodynamic therapy, which utilizes sonosensitizers to generate reactive oxygen species (ROS) under ultrasound (US) energy for antibacterial purposes, still lacks suitable sonosensitizers with good biocompatibility that can simultaneously promote the repair of various infected tissues. In this study, we constructed a novel sonosensitizer composed of hemoglobin derived from nature and zeolitic imidazolate framework (ZIF)-8, which exhibits excellent biocompatibility and activity. This sonosensitizer enables early-stage high-power US to generate substantial ROS for antibacterial effects and late-stage low-power sono-ionic therapy for tissue repair. We employed bone, wound infection, and wound biofilm models to evaluate the therapeutic efficacy in different infected tissues. We utilized microneedles to assemble nanoparticles to match the different disease models, achieving deep biofilm clearance. Furthermore, to investigate the repair mechanisms, we developed a bioadhesive-derived hydrogel loaded with nanoparticles for wound treatment. RNA sequencing revealed that sono-ionic therapy promotes tissue repair through the peroxisome proliferator-activated receptor signaling pathway. Therefore, our platform holds great potential for broad-spectrum treatment of infectious tissue repair.