A biomimetic calcium phosphate nanowire coating on titanium surface enhances osteoimmunomodulation and osteointegration

The appropriate immune microenvironment plays crucial roles in bone regeneration. Surface structure and chemistry are key factors affecting immune cells behavior and subsequently regulating the activity of bonerelated cells. To achieve rapid osteointegration, this study prepared a biomimetic calcium phosphate (CaP) coating on Ti-based substrates (THCaP) with the help of oleic acid under hydrothermal condition. The coating was composed of hydroxyapatite nanowires and further self-assembled into micropores. Also, the effect of the biomimetic CaP coating on the immune response of macrophages and the impact on angiogenesis and osteogenesis were investigated. In vitro cell culture results showed that compared with pristine Ti and similar titanate nanowire structure (TH), THCaP not only stimulated the polarization of macrophages towards a pro-healing M2 phenotype, but also enhanced the angiogenic and osteogenic differentiation of endothelial cells and preosteoblastic cells, respectively. Particularly, macrophages on THCaP induced a favorable immune microenvironment that facilitated osteogenic differentiation of pre-osteoblastic cells. In vivo tests confirmed these findings, showing that the implanted THCaP could suppress the inflammatory response and facilitate new bone formation when compared with pristine Ti and TH implants. These results indicate that preparation of biomimetic CaP network structure is a promising approach to surface design of Ti-based substrates, which is beneficial to generate a favorable osteoimmunomodulatory microenvironment for enhancing osteointegration.