Nanostructured Titanium for Improved Endothelial Biocompatibility and Reduced Platelet Adhesion in Stent Applications

Abstract

Although coronary stents have improved the early and long-term consequences of arterial lesions, the prevention of restenosis and late stent thrombosis is key to prevent a new obstruction of the vessel. Here we aimed at improving the tissue response to stents through surface modification. For that purpose, we used two different approaches, the use of nanostructuration by electrochemical anodization and the addition of a quercitrin (QR) coating to the Ti surface. Four surfaces (Ti, NN, TiQR and NNQR) were characterized by atomic force microscopy, scanning electronic microscopy and contact angle analysis and QR content was evaluated by fluorescent staining. Cell adhesion, cytotoxicity, metabolic activity and nitric oxide (NO) production was evaluated on primary human umbilical cord endothelial cells (HUVECs). Platelet adhesion, hemolysis rate and Staphylococcus epidermidis CECT 4184 adhesion at 30 min were analyzed. Nanostructuration induced an increase on surface roughness, and QR coating decreased the contact angle. All surfaces were biocompatible, with no hemolysis rate and lower platelet adhesion was found in NN surfaces. Finally, S. epidermidis adhesion was lower on TiQR surfaces compared to Ti. In conclusion, our results suggest that NN structuration could improve biocompatibility of bare metal stents on endothelial cells and reduce platelet adhesion. Moreover, QR coating could reduce bacterial adhesion.

Antithrombotic and hemocompatible properties of nanostructured coatings assembled from block copolymers

“…6A, blue). Nanotopography can affect the platelet behavio r [3,17,19,20] and indeed, fewer platelets were found on the nanopatterns generated by SVA in chloroform and similar adhesion was observed for their crosslinked analogs. The subsequent functionalization of these nanopatterns with heparin, known for its antithrombotic activity [29,56,60], reduced remarkably the adhesion (Fig.…”

“…In these cases, hemocompatibility is a major issue considering that the management of thrombus formation is still challenging [16]. Indeed, the hemocompatibility of micro-and nanostructured surfaces with chemically homogeneous composition has been already addressed [3,[17][18][19][20]. As an example, submicron structures generated by phase separation of polyurethane grafted with alkyl chains have shown a reduction of platelet adhesion [21].…”

Surface modification strategies to improve titanium hemocompatibility: a comprehensive review

“…131 Llopis-Grimalt et al modified the titanium surface to improve tissue response to stents using two different approaches, the use of nanostructuration by electrochemical anodization and the addition of quercitrin to the titanium surface. 132 Quercitrin, a glycoside formed from the flavonoid quercetin, has shown enhanced cell differentiation and anti-inflammatory activity when immobilized on titanium surfaces. 133 The surfaces were investigated for cell adhesion, cytotoxicity, nitic oxide production and metabolic activity using primary human umbilical cord endothelial cell.…”

Biomimetic Surface Topography from the Rubus fruticosus Leaf as a Guidance of Angiogenesis in Tissue Engineering Applications

“…A valuable strategy involves the use of physical and biochemical properties of the grafts used in TE approaches. Concerning the physical properties of scaffolds, it is well-known that they can modulate interfaces and directly influence the interaction and integration of the cells, mainly associated with induction of specific cellular signaling pathways. , As such, topography was already reported to play a key role in the endothelial cell behavior. , Several reports in the literature involving substrate topography for angiogenesis revealed to influence endothelial cell behavior, namely, in its proliferation, metabolic activity, morphology, migration, and secretion of cytokines and chemokines. − Depending on the topography of the substrate considered, endothelial cell proliferation and metabolic activity can be either positively or negatively affected by topography. As an example, human umbilical vein endothelial cells demonstrated to proliferate less on nanoscale topography when cultured on a substrate with ridges and grooves ranging from 400 to 800 nm when compared to its proliferation on a flat surface .…”