Osteoinduction-immunomodulation dual-functional calcium nervonate nanoparticles for promoting bone regeneration

Stem cell-based bone repair in vivo relies on both the osteogenic differentiation of stem cells and the immune activities of immune cells. The lack of effective means to simultaneously tune the local osteoinductive and inflammatory microenvironments is one of the major obstacles to the treatment of bone defects. Herein, we report calcium nervonate nanoparticles as a dual-functional therapeutic platform combining osteoinduction and immunomodulation for bone regeneration. Calcium nervonate nanoparticles will be decomposed into calcium ion (Ca2+) and nervonic acid in acidic lysosomes after being taken up by cells. The released Ca2+ and nervonic acid can then contribute to the osteogenic and anti-inflammatory microenvironments, respectively. In vitro experiments demonstrate that calcium nervonate nanoparticles promote the osteogenic differentiation of mesenchymal stem cells and alleviate the inflammatory response caused by lipopolysaccharide-activated macrophages. In vivo bone defect repair experiments confirm that calcium nervonate nanoparticles have better performance for promoting bone regeneration than Ca2+ or nervonic acid alone. This work develops a new bone regeneration approach by exploring calcium nervonate nanoparticles as a dual-functional platform, which has great promise in repairing bone defects.