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

Abstract

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 to 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.

Point‐of‐care seeding of nitinol stents with blood‐derived endothelial cells

“…The non‐significant increase in the expression level of these genes was likely due to the large coefficients of variation, which may reflect the range of shear stresses to which the ECs were exposed to on the stent struts. This notion was supported by other study demonstrating much smaller coefficients of variation in COX‐2 and KLF‐2 gene expression when ECs were exposed to flow on a planar Ti surface …”

“…This notion was supported by other study demonstrating much smaller coefficients of variation in COX-2 and KLF-2 gene expression when ECs were exposed to flow on a planar Ti surface. 24 The level of eNOS gene was downregulated after exposure of the cell-seeded stents to flow, but the secretion of NO as indicated by nitrite levels increased. In our previous work, we have observed that exposure of blood-derived and aortic hECs to flow shear stress (15 dyne/cm 2 for 24 h) caused an overall increase in eNOS gene expression.…”

Sub-100 nm patterning of TiO2film for the regulation of endothelial and smooth muscle cell functions

“…On the other hand, spatially arranged micron and submicron titanium features have been demonstrated to modulate vascular cell behavior. 15,16 Among the various choices of metallic materials, titanium-based alloys are the promising candidates for vascular intervention applications because of their excellent corrosion resistance, biocompatibility and mechanical properties [17][18][19] where corrosion resistance and biocompatibility mainly results from the TiO 2 passivation layer. [20][21][22] A thin layer of TiO 2 has also been shown to improve blood compatibility when coated on stainless steel.…”