Immunomodulation and osseointegration activities of Na₂TiO₃ nanorods-arrayed coatings doped with different Sr content

To endow Ti-based orthopedic implants immunomodulatory capability and thus enhanced osseointegration, different amounts of Sr are doped in Na₂TiO₃ nanorods in the arrays with identical nanotopographic parameters (rod diameter, length and inter-rod spacing) by substitution of Na⁺ using hydrothermal treatment. The obtained arrays are denoted as STSr2, STSr4, and STSr7, where the arabic numbers indicate the incorporating amounts of Sr in Na₂TiO₃. The modulation effects of the Sr-doped nanorods arrays on macrophage polarization and osteogenetic functions of osteoblasts are investigated, together with the array without Sr (ST). Moreover, osseointegration of these arrays are also assayed in rat femoral condyles. Sr-doped nanorods arrays accelerate M1 (pro-inflammatory phenotype)-to-M2 (anti-inflammatory phenotype) transformation of the adhered macrophages, enhancing secretion of pro-osteogenetic cytokines and growth factors (TGF-β1 and BMP2), moreover, the Sr doped arrays directly enhance osteogenetic functions of osteoblasts. The enhancement of paracrine of M2 macrophages and osteogenetic function of osteoblasts is promoted with the increase of Sr incorporating amounts. Consequently, Sr doped arrays show significantly enhanced osseointegration in vivo compared to ST, and STSr7 exhibits the best performance. Our work sheds a new light on the design of surface chemical components and structures for orthopedic implants to enhance their osseointegration.