Surface projections of titanium substrates increase antithrombotic endothelial function in response to shear stress

Despite the therapeutic benefits of both mechanical circulatory assist devices and nitinol stents with titanium (Ti) outer surfaces, problems remain with thrombosis at the blood-contacting surface. Covering these surfaces with a layer of endothelium would mimic the native lining of the cardiovascular system, potentially decreasing thrombotic complications. Since surface topography is known to affect the phenotype of a seeded cell layer and since stents and ventricular assist devices exhibit surface protrusions, we tested the hypothesis that endothelial cells (ECs) have altered function on Ti surfaces with protrusions of 1.25, 3, and 5 μm height, compared with smooth Ti surfaces. ECs and nuclei were more aligned and ECs were more elongated on all patterned surfaces. Cell area was reduced on the 3 and 5 μm features. Expression of eNOS and COX2 was not altered by patterned surfaces, but expression of KLF-2 was higher on 1.25 and 5 μm features. Nitric oxide production following exposure to flow was higher on the 5 μm features. These results show that some antithrombogenic functions of ECs are significantly enhanced for ECs cultured on surface protrusions, and no functions are diminished, informing the future design of implant surfaces for endothelialization.