Journal of The Royal Society Interface
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Macro- and microscale variables regulate stent haemodynamics, fibrin deposition and thrombomodulin expression

Juan M. Jiménez

Juan M. Jiménez

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA

[email protected]

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Varesh Prasad

Varesh Prasad

Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA

Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA

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Michael D. Yu

Michael D. Yu

Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA

Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA

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Christopher P. Kampmeyer

Christopher P. Kampmeyer

Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA

Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA

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Abdul-Hadi Kaakour

Abdul-Hadi Kaakour

Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA

Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA

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Pei-Jiang Wang

Pei-Jiang Wang

Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA

Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA

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Sean F. Maloney

Sean F. Maloney

Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA

Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA

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Nathan Wright

Nathan Wright

Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA

Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA

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Ian Johnston

Ian Johnston

Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA

Biomedical Graduate Studies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

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Yi-Zhou Jiang

Yi-Zhou Jiang

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA

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Peter F. Davies

Peter F. Davies

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA

Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA

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    Drug eluting stents are associated with late stent thrombosis (LST), delayed healing and prolonged exposure of stent struts to blood flow. Using macroscale disturbed and undisturbed fluid flow waveforms, we numerically and experimentally determined the effects of microscale model strut geometries upon the generation of prothrombotic conditions that are mediated by flow perturbations. Rectangular cross-sectional stent strut geometries of varying heights and corresponding streamlined versions were studied in the presence of disturbed and undisturbed bulk fluid flow. Numerical simulations and particle flow visualization experiments demonstrated that the interaction of bulk fluid flow and stent struts regulated the generation, size and dynamics of the peristrut flow recirculation zones. In the absence of endothelial cells, deposition of thrombin-generated fibrin occurred primarily in the recirculation zones. When endothelium was present, peristrut expression of anticoagulant thrombomodulin (TM) was dependent on strut height and geometry. Thinner and streamlined strut geometries reduced peristrut flow recirculation zones decreasing prothrombotic fibrin deposition and increasing endothelial anticoagulant TM expression. The studies define physical and functional consequences of macro- and microscale variables that relate to thrombogenicity associated with the most current stent designs, and particularly to LST.

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