Multifunctional CeO2 nanozymes for mitigating high-glucose induced senescence and enhancing bone regeneration in type 2 diabetes mellitus

Healing bone defects in patients with type 2 diabetes mellitus (T2DM) has long been a challenging issue. Elevated blood sugar levels in T2DM lead to the overproduction of reactive oxygen species (ROS), which negatively affects mitochondrial function, induces senescence in bone marrow mesenchymal stem cells (BMSCs), and diminishes their osteoblastic potential. In this study, we developed polyacrylic acid modified cerium oxide nanoparticles (PCNPs), a biocompatible, water-soluble, and antioxidant nanozyme. Our in vitro experiments demonstrated that PCNPs effectively eliminated ROS, restored mitochondrial function, and significantly upregulated the AMPK-SIRT1-PGC1α signaling pathway, ultimately mitigating BMSCs senescence. Considering clinical applications, we have also investigated the synergistic effects of PCNPs with material systems for sustained release in vivo. This sustained-release system proved to be more effective in mitigating BMSCs senescence and promoting bone defect healing in T2DM rats. These findings introduce a promising and innovative approach for managing bone defects in T2DM patients using customized multifunctional nanozymes.