Improved endothelial cell adhesion and proliferation on patterned titanium surfaces with rationally designed, micrometer to nanometer features

Previous in vitro studies have demonstrated increased vascular endothelial cell adhesion on random nanostructured titanium (Ti) surfaces compared with conventional (or nanometer smooth) Ti surfaces. These results indicated for the first time the potential nanophase metals have for improving vascular stent efficacy. However, considering the structural properties of the endothelium, which is composed of elongated vascular endothelial cells aligned with the direction of blood flow, it has been speculated that rationally designed, patterned nano-Ti surface features could further enhance endothelial cell functions by promoting a more native cellular morphology. To this end, patterned Ti surfaces consisting of periodic arrays of grooves with spacings ranging from 750 nm to 100 microm have been successfully fabricated in the present study by utilizing a novel plasma-based dry etching technique that enables machining of Ti with unprecedented resolution. In vitro rat aortic endothelial cell adhesion and growth assays performed on these substrates demonstrated enhanced endothelial cell coverage on nanometer-scale Ti patterns compared with larger micrometer-scale Ti patterns, as well as controls consisting of random nanostructured surface features. Furthermore, nanometer-patterned Ti surfaces induced endothelial cell alignment similar to the natural endothelium. Since the re-establishment of the endothelium on vascular stent surfaces is critical for stent success, the present study suggests that nanometer to submicrometer patterned Ti surface features should be further investigated for improving vascular stent efficacy.