Ultrasmall Pt nanoparticles modified bioenergetic-active implant for osteoporotic bone treatment via MSCs reprogramming and immunomodulation

Adenosine triphosphate (ATP) generation of the cells in osteoporosis microenvironment is inhibited by the high level of reactive oxygen species (ROS), and then results in the dysfunctions of stem cells and immune cells. Herein, we present a bioenergetic-active bone implant (TNT@Pt), which features TiO₂ nanotubes decorated with ultrasmall Pt nanoparticles on Ti surface. Thanks to the strong SOD-like and CAT-like enzymatic activities of ultrasmall Pt nanoparticles (3-4 nm), the TNT@Pt implant can scavenge ROS effectively, and then restore the mitochondrial membrane potential and recover ATP synthesis. The ATP produced by OVX BMSCs cultured on the surface of TNT@Pt samples increased by 108 %. With an enhanced ATP generation ability, the TNT@Pt implant induce a better bone differentiation of MSCs <i>via</i> activating PI3K-Akt, MAPK, and Calcium signaling pathways. Furthermore, the TNT@Pt implant can also enhance the ATP production of macrophage, and thus shifting its polarization to an anti-inflammatory phenotype, and finally mediating an improved osteogenic differentiation of BMSCs. Mouse air-pouch model and rat femur implantation model verify the superior immunomodulation and bone regeneration capabilities of the TNT@Pt implant <i>in vivo.</i> Collectively, the novel bioenergetic-active bone implant shows promising potential for the clinic treatment of osteoporotic bone defect.