A bypass flow model to study endothelial cell mechanotransduction across diverse flow environments

A bypass flow model to study endothelial cell mechanotransduction across diverse flow environments

Xiao, Zhuotao (Leiden University Medical Center; The First Affiliated Hospital of Soochow University)
Postma, Rudmer J. (Leiden University Medical Center)
van Zonneveld, Anton Jan (Leiden University Medical Center)
van den Berg, Bernard M. (Leiden University Medical Center)
Sol, Wendy M.P.J. (Leiden University Medical Center)
White, N.A. (TU Delft Medical Instruments & Bio-Inspired Technology; Leiden University Medical Center)
van de Stadt, Huybert J.F. (Leiden University Medical Center)
Mirza, Asad (Florida International University)
Wen, Jun (Southwest University of Science and Technology)
Bijkerk, Roel (Leiden University Medical Center)
Rotmans, J.I. (Leiden University Medical Center)

2024

Disturbed flow is one of the pathological initiators of endothelial dysfunction in intimal hyperplasia (IH) which is commonly seen in vascular bypass grafts, and arteriovenous fistulas. Various in vitro disease models have been designed to simulate the hemodynamic conditions found in the vasculature. Nonetheless, prior investigations have encountered challenges in establishing a robust disturbed flow model, primarily attributed to the complex bifurcated geometries and distinctive flow dynamics. In the present study, we aim to address this gap by introducing an in vitro bypass flow model capable of inducing disturbed flow and other hemodynamics patterns through a pulsatile flow in the same model. To assess the model's validity, we employed computational fluid dynamics (CFD) to simulate hemodynamics and compared the morphology and functions of human umbilical venous endothelial cells (HUVECs) under disturbed flow conditions to those in physiological flow or stagnant conditions. CFD analysis revealed the generation of disturbed flow within the model, pinpointing the specific location in the channel where the effects of disturbed flow were observed. High-content screening, a single-cell morphological profile assessment, demonstrated that HUVECs in the disturbed flow area exhibited random orientation, and morphological features were significantly distinct compared to cells in the physiological flow or stagnant condition after a two days of flow exposure. Furthermore, HUVECs exposed to disturbed flow underwent extensive remodeling of the adherens junctions and expressed higher levels of endothelial cell activation markers compared to other hemodynamic conditions. In conclusion, our in vitro bypass flow model provides a robust platform for investigating the associations between disturbed flow pattern and vascular diseases.

Computational fluid dynamics
Disturbed flow
High-content screening
In vitro model
Vascular bifurcation

http://resolver.tudelft.nl/uuid:2068aebf-f778-43de-86ce-5dd8680f1a1e

https://doi.org/10.1016/j.mtbio.2024.101121

2590-0064

Materials Today Bio, 27

Institutional Repository

journal article

© 2024 Zhuotao Xiao, Rudmer J. Postma, Anton Jan van Zonneveld, Bernard M. van den Berg, Wendy M.P.J. Sol, N.A. White, Huybert J.F. van de Stadt, Asad Mirza, Jun Wen, Roel Bijkerk, J.I. Rotmans