"Do-it-yourself in vitro vasculature that recapitulates in vivo geometries for investigating endothelial-blood cell interactions"

• Type of Material: Article
• Authors: Roger G. Mannino, Georgia Institute of Technology; David Myers, Emory University; Byungwook Ahn, Georgia Institute of Technology; Yichen Wang, Georgia Institute of Technology; Margo Rollins, Georgia Institute of Technology; Hope Gole, Georgia Institute of Technology; Angela S. Lin, Georgia Institute of Technology; Robert Guldberg, Emory University; Don Giddens, Emory University; Lucas Timmins, Emory University; Wilbur Lam, Emory University
• Language: English
• Date: 2015-07-23
• Publisher: Nature Publishing Group: Open Access Journals - Option C
• Publication Version: Final Published Version
• Copyright Statement: © 2015, Macmillan Publishers Limited
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/srep12401
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 5
• Start Page: 12401
• End Page: 12401
• Grant/Funding Information: Financial support for this work was provided by National Science Foundation CAREER Award 1150235 (to W.A.L.); an American Heart Association Innovative Research Grant (to W.A.L.); National Institutes of Health Grants 5U01-HL117721 (to W.A.L.), U54HL112309 (to W.A.L.), R01HL121264 (to W.A.L.); an American Heart Association Postdoctoral Fellowship (to D.R.M.); a National Science Foundation Graduate Research Fellowship (to R.G.M); and the Parker H. Petit Institute for Bioengineering and Bioscience Undergraduate Research Scholars Program (to P.W). D.R.M would like to acknowledge C.R.D for helpful discussions.
• Keywords: ERYTHROCYTES; CEREBRAL ANEURYSM; Multidisciplinary Sciences; POSTCAPILLARY VENULES; DISEASE; PLATELET-AGGREGATION; DISTURBED FLOW; BIFURCATION; WALL SHEAR-STRESS; SPATIAL GRADIENTS; Science & Technology; Science & Technology - Other Topics; SICKLE-CELL

Abstract

Investigating biophysical cellular interactions in the circulation currently requires choosing between in vivo models, which are difficult to interpret due in part to the hemodynamic and geometric complexities of the vasculature; or in vitro systems, which suffer from non-physiologic assumptions and/or require specialized microfabrication facilities and expertise. To bridge that gap, we developed an in vitro "do-it-yourself" perfusable vasculature model that recapitulates in vivo geometries, such as aneurysms, stenoses, and bifurcations, and supports endothelial cell culture. These inexpensive, disposable devices can be created rapidly (<2 hours) with high precision and repeatability, using standard off-the-shelf laboratory supplies. Using these "endothelialized" systems, we demonstrate that spatial variation in vascular cell adhesion molecule (VCAM-1) expression correlates with the wall shear stress patterns of vascular geometries. We further observe that the presence of endothelial cells in stenoses reduces platelet adhesion but increases sickle cell disease (SCD) red blood cell (RBC) adhesion in bifurcations. Overall, our method enables researchers from all disciplines to study cellular interactions in physiologically relevant, yet simple-to-make, in vitro vasculature models.