Interrod spacing dependent angiogenesis and osseointegration of Na2TiO3 nanorods-patterned arrays via immunoregulation

Nanorods-arrayed coatings show topographical parameters-dependent immunomodulation that plays a key role in angiogenesis and consequent osseoinegration, while immunomodulation by interrod spacing, as a solely altered topographic parameter of an array, has not been clarified yet. In this context, four kinds of nanorodsarrayed coatings, appearing similar surface roughness and hydrophilia, were hydrothermally grown on Ti. The coatings comprise a bilayer structure with compact nanogranular Na2TiO3 as an inner layer and Na2TiO3 nanorods-patterned array as an outer layer. The nanorods in the coatings exhibit identical rod diameter and length but different interrod spacing values of - 45, 75, 140, and 245 nm, respectively. Compared to Ti, the arrayed coatings promote adhesion and filopodia formation of macrophages to accelarate their transformation from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. Moreover, the accelaration is more pronounced by the coatings with nanoscale interrod spacing (especially - 75 nm) compared to those with submicro-scale spacing. The rapid phenotypic switch of macrophages on the arrayed coatings trigers the increase in their secretion of pro-angiogenic factors, including PDGF-BB, ANG1 and SDF-1, to enhance recruitment and angiogenesis of human umbilical vein endothelial cells (HUVECs) in co-culture condition, and the enhancment is the most pronounced for HUVECs in response to macrophages on - 75 nm spaced nanorods-arrayed coating. Owing to the favorable immune microenvironment induced by the coating and consequently enhanced angiogenesis, - 75 nm spaced nanorods-arrayed coating exhibits the best osseoinetegration in rat femoral condyles. Our work provides insights into the surface structural design of an orthopedic implant favoring osseointegration.