l-Arginine/nanofish bone nanocomplex enhances bone regeneration via antioxidant activities and osteoimmunomodulatory properties

Abstract In this study, a promising strategy has been developed to promote bone regeneration by combining antioxidant activities and osteoimmunomodulatory properties. Herein, an l -arginine/nanofish bone (Arg/NFB) nanocomplex has been prepared and evaluated in vitro and in vivo. The Arg/NFB nanocomplex possesses good antioxidant activities and could modulate the polarization of non-activated macrophage into different types and induce the secretion of pre-inflammatory, anti-inflammatory, osteogenic as well as angiogenic cytokines. Additionally, the regulated immune microenvironment can enhance the osteogenic differentiation of mouse embryo osteoblast precursor cells (MC3T3-E1) and angiogenic capacity of human umbilical vein endothelial cells (HUVECs), leading to the improved formation of mineralized nodules, alkaline phosphatase activity and angiogenic effects. In vivo results with cranial defect models reveal that the treatment of Arg/NFB nanocomplex exhibited significant improvement of new bone formation and angiogenesis. All the results demonstrate Arg/NFB nanocomplex with antioxidant activities and osteoimmunomodulatory properties could be a new idea for developing the next generation of bone regeneration biomaterials.