Spatiotemporal Sonodynamic‐Nanozymic Therapy for Infected Jawbone Defects

ABSTRACT Infectious jawbone defects, arising from open fractures, surgical contamination, or hematogenous pathogen spread, represent severe orthopedic complications characterized by concurrent bone loss and chronic infection. Precise control of pathogen colonization, effective modulation of local immune microenvironment, and activation of osteogenesis are spatiotemporal phases that pose significant clinical challenges. Here, we construct a multifunctional platform of copper‐zinc bimetallic metal–organic nanosheets encapsulated in a polyvinylpyrrolidone‐polyvinyl alcohol hydrogel (CuZn‐MON@gel). Upon ultrasound irradiation, CuZn‐MON produces singlet oxygen, achieving antibacterial efficiencies of 99.93% against Staphylococcus aureus and 99.78% against Porphyromonas gingivalis . In the absence of ultrasound, the nanozyme switches to SOD‐ and CAT‐like activities, scavenging excess reactive oxygen species and downregulating pro‐inflammatory pathways, including chemokine and NF‐κB signaling pathway. Simultaneously, controlled release of osteogenic Cu 2+ and Zn 2+ ions activates AMPK and PI3K/Akt pathways, enhancing the expression of osteogenic markers Runx2, ALP, OCN, and OPN. This system promotes osteogenic differentiation and accelerates bone regeneration in an infected rat model, achieving robust repair of jawbone defects. By dynamically balancing bactericidal ROS generation and antioxidant protection, CuZn‐MON@gel offers a spatiotemporal therapeutic strategy for reconstructing infectious bone defects.