Micro-engineered perfusable 3D vasculatures for cardiovascular diseases

Vessel geometries in microengineered in vitro vascular models are important to recapitulate a pathophysiological microenvironment for the study of flow-induced endothelial dysfunction and inflammation in cardiovascular diseases. Herein, we present a simple and novel extracellular matrix (ECM) hydrog...

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Main Authors: Menon, Nishanth Venugopal, Tay, Hui Min, Wee, Soon Nan, Li, King Ho Holden, Hou, Han Wei
Other Authors: School of Chemical and Biomedical Engineering
Format: Journal Article
Language:English
Published: 2017
Subjects:
Online Access:https://hdl.handle.net/10356/84344
http://hdl.handle.net/10220/43579
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author Menon, Nishanth Venugopal
Tay, Hui Min
Wee, Soon Nan
Li, King Ho Holden
Hou, Han Wei
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Menon, Nishanth Venugopal
Tay, Hui Min
Wee, Soon Nan
Li, King Ho Holden
Hou, Han Wei
author_sort Menon, Nishanth Venugopal
collection NTU
description Vessel geometries in microengineered in vitro vascular models are important to recapitulate a pathophysiological microenvironment for the study of flow-induced endothelial dysfunction and inflammation in cardiovascular diseases. Herein, we present a simple and novel extracellular matrix (ECM) hydrogel patterning method to create perfusable vascularized microchannels of different geometries based on the concept of capillary burst valve (CBV). No surface modification is necessary and the method is suitable for different ECM types including collagen, matrigel and fibrin. We first created collagen-patterned, endothelialized microchannels to study barrier permeability and neutrophil transendothelial migration, followed by the development of a biomimetic 3D endothelial-smooth muscle cell (EC-SMC) vascular model. We observed a significant decrease in barrier permeability in the co-culture model during inflammation, which indicates the importance of perivascular cells in ECM remodeling. Finally, we engineered collagen-patterned constricted vascular microchannels to mimic stenosis in atherosclerosis. Whole blood was perfused (1-10 dyne cm-2) into the microdevices and distinct platelet and leukocyte adherence patterns were observed due to increased shear stresses at the constriction, and an additional convective flow through the collagen. Taken together, the developed hydrogel patterning technique enables the formation of unique pathophysiological architectures in organ-on-chip microsystems for real-time study of hemodynamics and cellular interactions in cardiovascular diseases.
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spelling ntu-10356/843442020-11-01T05:30:40Z Micro-engineered perfusable 3D vasculatures for cardiovascular diseases Menon, Nishanth Venugopal Tay, Hui Min Wee, Soon Nan Li, King Ho Holden Hou, Han Wei School of Chemical and Biomedical Engineering School of Mechanical and Aerospace Engineering Lee Kong Chian School of Medicine (LKCMedicine) 3D Vasculatures Cardiovascular Diseases Vessel geometries in microengineered in vitro vascular models are important to recapitulate a pathophysiological microenvironment for the study of flow-induced endothelial dysfunction and inflammation in cardiovascular diseases. Herein, we present a simple and novel extracellular matrix (ECM) hydrogel patterning method to create perfusable vascularized microchannels of different geometries based on the concept of capillary burst valve (CBV). No surface modification is necessary and the method is suitable for different ECM types including collagen, matrigel and fibrin. We first created collagen-patterned, endothelialized microchannels to study barrier permeability and neutrophil transendothelial migration, followed by the development of a biomimetic 3D endothelial-smooth muscle cell (EC-SMC) vascular model. We observed a significant decrease in barrier permeability in the co-culture model during inflammation, which indicates the importance of perivascular cells in ECM remodeling. Finally, we engineered collagen-patterned constricted vascular microchannels to mimic stenosis in atherosclerosis. Whole blood was perfused (1-10 dyne cm-2) into the microdevices and distinct platelet and leukocyte adherence patterns were observed due to increased shear stresses at the constriction, and an additional convective flow through the collagen. Taken together, the developed hydrogel patterning technique enables the formation of unique pathophysiological architectures in organ-on-chip microsystems for real-time study of hemodynamics and cellular interactions in cardiovascular diseases. MOE (Min. of Education, S’pore) MOH (Min. of Health, S’pore) Accepted version 2017-08-14T07:08:13Z 2019-12-06T15:43:11Z 2017-08-14T07:08:13Z 2019-12-06T15:43:11Z 2017 Journal Article Menon, N. V., Tay, H. M., Wee, S. N., Li, K. H. H., & Hou, H. W. (2017). Micro-engineered perfusable 3D vasculatures for cardiovascular diseases. Lab on a Chip. 1473-0197 https://hdl.handle.net/10356/84344 http://hdl.handle.net/10220/43579 10.1039/C7LC00607A en Lab on a Chip © 2017 The Author(s) (Royal Society of Chemistry). This is the author created version of a work that has been peer reviewed and accepted for publication by Lab on a Chip, The Author(s) (Royal Society of Chemistry). It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1039/C7LC00607A]. 9 p. application/pdf
spellingShingle 3D Vasculatures
Cardiovascular Diseases
Menon, Nishanth Venugopal
Tay, Hui Min
Wee, Soon Nan
Li, King Ho Holden
Hou, Han Wei
Micro-engineered perfusable 3D vasculatures for cardiovascular diseases
title Micro-engineered perfusable 3D vasculatures for cardiovascular diseases
title_full Micro-engineered perfusable 3D vasculatures for cardiovascular diseases
title_fullStr Micro-engineered perfusable 3D vasculatures for cardiovascular diseases
title_full_unstemmed Micro-engineered perfusable 3D vasculatures for cardiovascular diseases
title_short Micro-engineered perfusable 3D vasculatures for cardiovascular diseases
title_sort micro engineered perfusable 3d vasculatures for cardiovascular diseases
topic 3D Vasculatures
Cardiovascular Diseases
url https://hdl.handle.net/10356/84344
http://hdl.handle.net/10220/43579
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