Prussian Blue Nanoparticles Promoting Diabetic Bone Regeneration via Mitochondrial Recovery

<b>Objective:</b> This work aims to develop Prussian blue (PB) nanoparticles that mitigate bone marrow mesenchymal stem cell (BMSC) senescence and alleviate bone loss in type 2 diabetes (T2D). <b>Impact Statement:</b> PB nanozymes are established as a targeted therapeutic strategy for maintaining bone quality in T2D-addressing an unmet clinical need through innovative nanomaterial design. <b>Introduction:</b> Diabetes is associated with a higher risk of fractures through distinct mechanisms. Elevated blood sugar levels and excessive nutrition in T2D trigger reactive oxygen species (ROS) overproduction that impairs mitochondrial function, induces BMSC senescence, and compromises osteogenic potential. Engineered as artificial enzyme counterparts, nanozymes effectively eliminate ROS while circumventing the inherent constraints of natural antioxidant enzymes. <b>Methods:</b> PB nanoparticles were synthesized and fully characterized. BMSCs treated with high glucose plus palmitate-bovine serum albumin served as the diabetic cell model. The nanoparticles were evaluated for their capacity to scavenge ROS, modulate mitochondrial function, counteract cellular senescence, and restore osteogenic potential. Finally, their ability to attenuate bone loss was verified in a T2D mouse model. <b>Results:</b> We demonstrated that PB nanoparticles efficiently scavenge ROS, rebalance mitochondrial dynamics by up-regulating fusion proteins and down-regulating fission proteins, and restore membrane potential. These actions suppress BMSC senescence and revive osteogenic capacity, culminating in substantial attenuation of T2D-associated bone loss in vivo. <b>Conclusion:</b> These findings introduce a promising and innovative approach for managing bone quality in patients with T2D.