A new microfluidic model that allows monitoring of complex vascular structures and cell interactions in a 3D biological matrix
van Dijk, Christian G M; Brandt, Maarten M; Poulis, Nikolaos; Anten, Jonas; van der Moolen, Matthijs; Kramer, Liana; Homburg, Erik F G A; Louzao-Martinez, Laura; Pei, Jiayi; Krebber, Merle M; van Balkom, Bas W M; de Graaf, Petra; Duncker, Dirk J; Verhaar, Marianne C; Luttge, Regina; Cheng, Caroline
(2020) Lab on a chip, volume 20, issue 10, pp. 1827 - 1844
(Article)
Abstract
Microfluidic organ-on-a-chip designs are used to mimic human tissues, including the vasculature. Here we present a novel microfluidic device that allows the interaction of endothelial cells (ECs) with pericytes and the extracellular matrix (ECM) in full bio-matrix encased 3D vessel structures (neovessels) that can be subjected to continuous, unidirectional flow
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and perfusion with circulating immune cells. We designed a polydimethylsiloxane (PDMS) device with a reservoir for a 3D fibrinogen gel with pericytes. Open channels were created for ECs to form a monolayer. Controlled, continuous, and unidirectional flow was introducedviaa pump system while the design facilitated 3D confocal imaging. In this vessel-on-a-chip system, ECs interact with pericytes to create a human cell derived blood vessel which maintains a perfusable lumen for up to 7 days. Dextran diffusion verified endothelial barrier function while demonstrating the beneficial role of supporting pericytes. Increased permeability after thrombin stimulation showed the capacity of the neovessels to show natural vascular response. Perfusion of neovessels with circulating THP-1 cells demonstrated this system as a valuable platform for assessing interaction between the endothelium and immune cells in response to TNFa. In conclusion: we created a novel vascular microfluidic device that facilitates the fabrication of an array of parallel soft-channel structures in ECM gel that develop into biologically functional neovessels without hard-scaffold support. This model provides a unique tool to conduct livein vitroimaging of the human vasculature during perfusion with circulating cells to mimic (disease) environments in a highly systematic but freely configurable manner.
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Keywords: Bioengineering, General Chemistry, Biochemistry, Biomedical Engineering, Journal Article
ISSN: 1473-0189
Publisher: Royal Society of Chemistry
Note: Funding Information: We would like to thank Dr. O. G. de Jong for donating lentiviral GFP and dsRED constructs. This work was supported by Netherlands Foundation for Cardiovascular Excellence [C. C.], Netherlands Organization for Scientific Research Vidi grant [no. 91714302 to C. C.] and Material Driven Regeneration Consortium [Gravitation program to C. C., M. V.], the Erasmus MC fellowship grant [C. C.], the Regenerative Medicine Fellowship grant of the University Medical Center Utrecht [C. C.], and the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation [CVON2014-11 RECONNECT to C. C., D. D., and M. V.]. Publisher Copyright: © The Royal Society of Chemistry 2020. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
(Peer reviewed)