A Glutathione Peroxidase‐Mimicking Nanozyme Precisely Alleviates Reactive Oxygen Species and Promotes Periodontal Bone Regeneration

The use of oxidoreductase nanozymes to regulate reactive oxygen species (ROS) has gradually emerged in periodontology treatments. However, current nanozymes for treating periodontitis eliminate ROS extensively and non‐specifically, ignoring the physiological functions of ROS under normal conditions, which may result in uncontrolled side effects. Herein, using the MIL‐47(V)‐F (MVF) nanozyme, which mimics the function of glutathione peroxidase (GPx), it is proposed that ROS can be properly regulated by specifically eliminating H2O2, the most prominent ROS. Through H2O2elimination, MVF contributes to limiting inflammation, regulating immune microenvironment, and promoting periodontal regeneration. Moreover, MVF stimulates osteogenic differentiation of periodontal stem cells directly, further promoting regeneration due to the vanadium in MVF. Mechanistically, MVF regulates ROS by activating the nuclear factor erythroid 2‐related factor 2/heme oxygenase 1 (Nrf2/HO‐1) pathway and promotes osteogenic differentiation directly through the phosphatidylinositol 3‐kinase/protein kinase B (PI3K/Akt) pathway. A promising periodontitis therapy strategy is presented using GPx‐mimicking nanozymes through their triple effects of antioxidation, immunomodulation, and bone remodeling regulation, making nanozymes an excellent tool for developing precision medicine. A GPx‐mimicking nanozyme, MVF, is developed and its selective clearance of H2O2is demonstrated. The experimental findings elucidate the triple functionality of MVF in regulating ROS, macrophage polarization, and the balance between osteogenesis and osteoclastogenesis, ultimately leading to the repair and regeneration of periodontal bone tissue.