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Design and Fabrication of a Three-Dimensional In Vitro System for Modeling Vascular Stenosis

Published online by Cambridge University Press:  17 July 2017

Rebecca S. Jones ,
Pin H. Chang ,
Tzlil Perahia ,
Katrina A. Harmon ,
Lorain Junor ,
Michael J. Yost ,
Daping Fan ,
John F. Eberth  and
Richard L. Goodwin
Rebecca S. Jones
Affiliation:
Biomedical Engineering Program, College of Engineering and Computing, University of South Carolina, Columbia, SC 29208, USA Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29209, USA
Pin H. Chang
Affiliation:
Biomedical Engineering Program, College of Engineering and Computing, University of South Carolina, Columbia, SC 29208, USA Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29209, USA
Tzlil Perahia
Affiliation:
Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29209, USA
Katrina A. Harmon
Affiliation:
Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29209, USA
Lorain Junor
Affiliation:
Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29209, USA
Michael J. Yost
Affiliation:
Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA
Daping Fan
Affiliation:
Biomedical Engineering Program, College of Engineering and Computing, University of South Carolina, Columbia, SC 29208, USA Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29209, USA
John F. Eberth
Affiliation:
Biomedical Engineering Program, College of Engineering and Computing, University of South Carolina, Columbia, SC 29208, USA Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29209, USA
Richard L. Goodwin*
Affiliation:
Department of Biomedical Sciences, School of Medicine, University of South Carolina, Greenville, SC 29605, USA
*
*Corresponding author. rlgoodwin@sc.edu
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Abstract

Vascular stenosis, the abnormal narrowing of blood vessels, arises from defective developmental processes or atherosclerosis-related adult pathologies. Stenosis triggers a series of adaptive cellular responses that induces adverse remodeling, which can progress to partial or complete vessel occlusion with numerous fatal outcomes. Despite its severity, the cellular interactions and biophysical cues that regulate this pathological progression are poorly understood. Here, we report the design and fabrication of a three-dimensional (3D) in vitro system to model vascular stenosis so that specific cellular interactions and responses to hemodynamic stimuli can be investigated. Tubular cellularized constructs (cytotubes) were produced, using a collagen casting system, to generate a stenotic arterial model. Fabrication methods were developed to create cytotubes containing co-cultured vascular cells, where cell viability, distribution, morphology, and contraction were examined. Fibroblasts, bone marrow primary cells, smooth muscle cells (SMCs), and endothelial cells (ECs) remained viable during culture and developed location- and time-dependent morphologies. We found cytotube contraction to depend on cellular composition, where SMC-EC co-cultures adopted intermediate contractile phenotypes between SMC- and EC-only cytotubes. Our fabrication approach and the resulting artery model can serve as an in vitro 3D culture system to investigate vascular pathogenesis and promote the tissue engineering field.

Keywords

collagenvascular stenosisbioreactorarterial modelin vitro culture
Type
Biological Science Applications
Information
Microscopy and Microanalysis , Volume 23 , Issue 4 , August 2017 , pp. 859 - 871
Copyright
© Microscopy Society of America 2017 

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Footnotes

†

Current address: Department of Civil and Environmental Engineering, College of Engineering, University of Michigan, Ann Arbor, MI 48109, USA.

‡

Current address: Department of Emergency Medicine, Crozer-Chester Medical Center, Upland, PA 19013, USA.

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