Hierarchically porous calcium-silicon nanosphere-enabled co-delivery of microRNA-210 and simvastatin for bone regeneration.

The regenerative repair of large bone defects is a major problem in orthopedics and clinical medicine. The key problem is the lack of ability of existing bone graft materials to promote osteogenesis and angiogenesis. Previous studies have shown that the osteogenic or angiogenic abilities of these materials could be significantly improved by adding miRNA or small-molecule drugs to bone graft materials; however, the synergistic effect arising from this combination is not clear. Therefore, we proposed to construct a dual drug delivery system that could simultaneously achieve the co-encapsulation and co-delivery of miRNA and small-molecule drugs to explore the effect of a dual drug delivery system on bone repair. In this study, we constructed dual-sized pore structure calcium-silicon nanospheres (DPNPs) and achieved the co-encapsulation of miR-210, angiogenic gene drugs, and simvastatin (Siv), a small-molecule osteogenic drug, through metal-ion coordination and physical adsorption. In vitro and in vivo osteogenic and angiogenic experiments showed that the dual drug delivery system (Siv/DPNP/miR-210) exhibited better properties than those of the individual unloaded and single drug-loaded systems and could significantly accelerate the process of bone repair, which provides a novel strategy for the regeneration and repair of bone defects.