Affiliations: Laboratory of Molecular Cardiology, Department of Cardiology and Angiology, University Hospital Erlangen, Erlangen, Germany | Max Schaldach-Stiftungsprofessur for Biomedical Engineering, University of Erlangen-Nuremberg, Erlangen, Germany | Cardiovascular Nanomedicine Unit, Section of Experimental Oncology and Nanomedicine, Else Kröner-Fresenius Stiftungsprofessur for Nanomedicine, University Hospital Erlangen, Erlangen, Germany
Note: [] These authors contributed to the work equally.
Note: [] These authors contributed to the work equally.
Note: [] Corresponding author: Iwona Cicha, PhD, Cardiovascular Nanomedicine Unit, Section of Experimental Oncology and Nanomedicine, ENT Department, University of Erlangen-Nuremberg, Glückstr. 10a, 91054 Erlangen, Germany. Tel.: +49 9131 8543953; Fax: +49 9131 8534282; E-mail: [email protected]
Abstract: 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.
