Effect of specific surface microstructures on substrate endothelialisation and thrombogenicity: Importance for stent design.

BACKGROUND: In coronary artery disease, highly stenosed arteries are frequently treated by stent implantation, which thereafter necessitates a dual-antiplatelet therapy (DAPT) in order to prevent stent-thrombosis. We hypothesized that specific patterns of microstructures on stents can accelerate endothelialisation thereby reducing their thrombogenicity and the DAPT duration. METHODS: Differently designed, 2-5 µm high elevations or hollows were lithographically etched on silicon plates, subsequently coated with silicon carbide. Smooth silicon plates and bare metal substrates were used as controls. To assess attachment and growth of human umbilical vein endothelial cells under static or flow conditions, actin cytoskeleton was visualised with green phalloidin. Endothelial migration was assessed in a modified barrier assay. To investigate surface thrombogenicity, platelets were incubated on the structured surfaces in static and flow conditions, and visualised with fluorescein-conjugated P-selectin antibody. Images were taken with incident-light fluorescent microscope for non-transparent objects. RESULTS: Compared to smooth surface, flat cubic elevations (5 µm edge length) improved endothelial cell attachment and growth under static and dynamic conditions, whereas smaller, spiky structures (2 µm edge length) had a negative influence on endothelialisation. Endothelial cell migration was fastest on flat cubic elevations, hollows, and smooth surfaces, whereas spiky structures and bare metal had a negative effect on endothelial migration. Thrombogenicity assays under static and flow conditions showed that platelet adhesion was reduced on the flat elevations and the smooth surface, as compared to the spiky structures, the hollow design and the bare metal substrates. CONCLUSION: Surface microstructures strongly influence endothelialisation of substrates. Designing stents with surface topography which accelerates endothelialisation and reduces thrombogenicity may be of clinical benefit by improving the safety profile of coronary interventions.

Differences of platelet adhesion and thrombus activation on amorphous silicon carbide, magnesium alloy, stainless steel, and cobalt chromium stent surfaces.

BACKGROUND: Coronary stenting is considered to be the gold standard of percutaneous coronary interventions, because stents are able to reduce early and late elastic recoil (negative remodeling) and restenosis in comparison with balloon angioplasty alone. OBJECTIVE: It is known that stent thrombogenicity and neointimal formation are determined by the surface characteristics of the stent platform, electrochemical features of the stent surface, and the degree of degradation after implantation. Metallic stents coated with amorphous silicon carbide and biodegradable stents made of magnesium alloy have been introduced clinically, but there are no data available comparing the biocompatibility of these novel stent materials with conventional stents. METHODS: We demonstrate simple and reproducible in vitro methods assessing the rate of platelet adhesion and thrombus activation for biocompatibility tests of different stent surfaces. RESULTS: We show that amorphous silicon carbide and magnesium alloy stent surfaces markedly lower the rate of platelet adhesion and platelet/fibrin activation when compared with uncoated stainless steel or cobalt chromium alloy surfaces. Semiconductor materials on the stent surface reduce platelet and fibrin activation by increasing the critical electron gap to greater than 0.9 eV resulting in a lower electron transfer out of the stent material. CONCLUSION: Passive stent coatings with specific semiconducting properties such as amorphous silicon carbide or magnesium alloy reduce thrombogenicity and may improve biocompatibility of a stent platform.