Narrow window in nanoscale dependent activation of endothelial cell growth and differentiation on TiO2 nanotube surfaces.

Critical features of biomimetic materials used for vascular grafts and stents are surface structure and chemical features of the implant material supporting adhesion, proliferation, and differentiation of endothelial cells and smooth muscle cells, the major cell types of blood vessels. Recently, experimental evidence from several laboratories have indicated a strong stimulation of cellular activities on vertically aligned TiO(2) nanotube surfaces in comparison to amorphous TiO(2) surfaces. Conflicting reports exist, however, concerning the nanoscale dimension, and the role of the chemistry and crystallinity of the nanotubes in eliciting cell responses. Here we demonstrate that 15 nm nanotubes provide a substantially stronger stimulation of differentiation of mesenchymal cells to endothelial cells and smooth muscle cells than 70-100 nm nanotubes, while high rates of apoptosis were seen on 100 nm nanotubes. Also endothelial cell adhesion, proliferation, and motility were several-fold higher on 15 nm than on 100 nm nanotubes. Furthermore, our data indicate a clear dominance of the nanoscale geometry on endothelial cell behavior over surface chemistry and crystallinity of the TiO(2) nanotube surface. These findings indicate that fine-tuning of TiO(2) surfaces at nanoscale will be an essential parameter in optimizing endothelial cell and smooth muscle cell responses to vascular implants.