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A Pulsatile Flow System to Engineer Aneurysm and Atherosclerosis Mimetic Extracellular Matrix.

  • Hosseini V Laboratory of Applied Mechanobiology Institute of Translational Medicine Department of Health Sciences and Technology ETH Zurich Zurich 8093 Switzerland.
  • Mallone A Institute for Regenerative Medicine (IREM) University of Zurich and Wyss Translational Center Zurich Zurich 8952 Switzerland.
  • Mirkhani N Responsive Biomedical Systems Lab Institute of Translational Medicine Department of Health Sciences and Technology ETH Zurich Zurich 8093 Switzerland.
  • Noir J Institute of Geophysics Department of Earth Sciences ETH Zurich Zurich 8092 Switzerland.
  • Salek M Department of Mechanical Engineering Massachusetts Institute of Technology Boston MA 02139 USA.
  • Pasqualini FS Institute for Regenerative Medicine (IREM) University of Zurich and Wyss Translational Center Zurich Zurich 8952 Switzerland.
  • Schuerle S Responsive Biomedical Systems Lab Institute of Translational Medicine Department of Health Sciences and Technology ETH Zurich Zurich 8093 Switzerland.
  • Khademhosseini A Department of Bioengineering University of California-Los Angeles Los Angeles CA 90095 USA.
  • Hoerstrup SP Institute for Regenerative Medicine (IREM) University of Zurich and Wyss Translational Center Zurich Zurich 8952 Switzerland.
  • Vogel V Laboratory of Applied Mechanobiology Institute of Translational Medicine Department of Health Sciences and Technology ETH Zurich Zurich 8093 Switzerland.
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  • 2020-06-30
Published in:
  • Advanced science (Weinheim, Baden-Wurttemberg, Germany). - 2020
aneurysms
arterial wall diseases
atherosclerosis
extracellular matrix
human vascular smooth muscle cells
in vitro 3D tissue models
pulsatile flow
English 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.
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  • English
Open access status
gold
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https://sonar.ch/global/documents/50622
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