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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)\u20108, which exhibits excellent biocompatibility and activity. This sonosensitizer enables early\u2010stage high\u2010power US to generate substantial ROS for antibacterial effects and late\u2010stage low\u2010power sono\u2010ionic 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\u2010derived hydrogel loaded with nanoparticles for wound treatment. RNA sequencing revealed that sono\u2010ionic therapy promotes tissue repair through the peroxisome proliferator\u2010activated receptor signaling pathway. Therefore, our platform holds great potential for broad\u2010spectrum treatment of infectious tissue repair.<\/jats:p>","DOI":"10.1002\/exp2.70208","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T03:23:08Z","timestamp":1786418588000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Engineered Nature\u2010Based Sonosensitizer for Broad\u2010Spectrum Infectious Tissue Repair via Sono\u2010Ionic Therapy"],"prefix":"10.1002","volume":"6","author":[{"given":"Liang","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Union Hospital Tongji Medical College Huazhong University of Science and 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