A Pulsatile Flow System to Engineer Aneurysm and Atherosclerosis Mimetic Extracellular Matrix
OPEN ACCESS
Loading...
Author / Producer
Date
2020-06
Publication Type
Journal Article
ETH Bibliography
yes
Citations
Altmetric
OPEN ACCESS
Data
Rights / License
Abstract
Alterations of blood flow patterns strongly correlate with arterial wall diseases such as atherosclerosis and aneurysm. Here, a simple, pumpless, close‐loop, easy‐to‐replicate, and miniaturized flow device is introduced to concurrently expose 3D engineered vascular smooth muscle tissues to high‐velocity pulsatile flow versus low‐velocity disturbed flow conditions. Two flow regimes are distinguished, one that promotes elastin and impairs collagen I assembly, while the other impairs elastin and promotes collagen assembly. This latter extracellular matrix (ECM) composition shares characteristics with aneurysmal or atherosclerotic tissue phenotypes, thus recapitulating crucial hallmarks of flow‐induced tissue morphogenesis in vessel walls. It is shown that the mRNA levels of ECM of collagens and elastin are not affected by the differential flow conditions. Instead, the differential gene expression of matrix metalloproteinase (MMP) and their inhibitors (TIMPs) is flow‐dependent, and thus drives the alterations in ECM composition. In further support, treatment with doxycycline, an MMP inhibitor and a clinically used drug to treat vascular diseases, halts the effect of low‐velocity flow on the ECM remodeling. This illustrates how the platform can be exploited for drug efficacy studies by providing crucial mechanistic insights into how different therapeutic interventions may affect tissue growth and ECM assembly.
Permanent link
Publication status
published
External links
Editor
Book title
Journal / series
Volume
7 (12)
Pages / Article No.
2000173
Publisher
Wiley
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
aneurysms; arterial wall diseases; atherosclerosis; extracellular matrix; human vascular smooth muscle cells; in vitro 3D tissue models; pulsatile flow
Organisational unit
03640 - Vogel, Viola (emeritus) / Vogel, Viola (emeritus)
09619 - Schürle-Finke, Simone / Schürle-Finke, Simone
03734 - Jackson, Andrew / Jackson, Andrew
Notes
Funding
175839 - Mechanobiology of Extracellular Matrix (SNF)
165641 - Understanding planetary magnetic fields from theoretical, numerical and analogue models (SNF)
165641 - Understanding planetary magnetic fields from theoretical, numerical and analogue models (SNF)