title: The influence of surface micro-structure on endothelialization under supraphysiological wall shear stress.
abstract: Interaction between platelets and artificial materials within cardiovascular devices triggers blood coagulation and represents a frequent adverse response to implant deployment. Avoidance of this interaction is obtained through the generation and sustenance under flow of a confluent and stable endothelial monolayer covering the luminal device surface, altogether defined as the process of endothelialization. Supraphysiological wall shear stress (WSS) levels generated within vascular assist devices (VADs) constitute a major challenge toward endothelialization. Here we report the experimental demonstration that stable endothelialization can be achieved at supraphysiological WSS levels by pure means of appropriate surface micro-structuring. Using a custom-designed flow bioreactor we exposed endothelial monolayers to physiological and supraphysiological WSS levels and investigated the resulting integrity of cell-to-cell junctions, the cell density and the cell polarization. At physiological WSS levels, optimal endothelialization was obtained independently from surface topography. However, at higher WSS levels, only monolayers grown on appropriately micro-structured surfaces preserved optimal integrity. Under these flow conditions, endothelial cells polarized by the contact with the micro-structure and, interestingly, oriented themselves in the direction perpendicular to flow. Such endothelial layers withstood WSS levels exceeding of 100% or more the thresholds detected on flat substrates.
authors.affiliation: Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, Sonneggstrasse 3, 8092 Zurich, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Robotti
authors.affiliation: Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, Sonneggstrasse 3, 8092 Zurich, Switzerland; Clinic of Cardiac and Vascular Surgery, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Davide
authors.initials: D
authors.lastname: Franco
authors.affiliation: Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, Sonneggstrasse 3, 8092 Zurich, Switzerland.
authors.forename: Livia
authors.initials: L
authors.lastname: Bänninger
authors.affiliation: Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, Sonneggstrasse 3, 8092 Zurich, Switzerland.
authors.forename: Jair
authors.initials: J
authors.lastname: Wyler
authors.affiliation: Clinic of Cardiac and Vascular Surgery, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Christoph T
authors.initials: CT
authors.lastname: Starck
authors.affiliation: Clinic of Cardiac and Vascular Surgery, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Falk
authors.affiliation: Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, Sonneggstrasse 3, 8092 Zurich, Switzerland.
authors.forename: Dimos
authors.initials: D
authors.lastname: Poulikakos
authors.affiliation: Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, Sonneggstrasse 3, 8092 Zurich, Switzerland. Electronic address: aferrari@ethz.ch.
authors.forename: Aldo
authors.initials: A
authors.lastname: Ferrari
mesh_terms: D019149:Bioreactors; D016764:Cell Polarity; D004730:Endothelium, Vascular / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D044085:Microfluidics; D015203:Reproducibility of Results; D033081:Shear Strength; D013314:Stress, Mechanical; D013499:Surface Properties
keywords: Adhesion; Endothelial cells; Endothelialization; Topography; Vascular endothelial cadherin; Wall shear stress