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Research Papers

A Novel Multiwell Device to Study Vascular Smooth Muscle Cell Responses Under Cyclic Strain

[+] Author and Article Information
Uday Tata, Smitha M. N. Rao

Department of Electrical Engineering, University of Texas at Arlington, Arlington, TX 76019

Hao Xu

 Dallas Veterans Affairs Medical Center, Dallas, TX 75216; Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019

Cheng-Jen Chuong, Kytai T. Nguyen

Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019

J.-C. Chiao1

Department of Electrical Engineering, and Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019jcchiao@uta.edu

1

Corresponding author.

J. Nanotechnol. Eng. Med 2(2), 021007 (May 16, 2011) (6 pages) doi:10.1115/1.4003928 History: Received March 08, 2011; Revised March 15, 2011; Published May 16, 2011; Online May 16, 2011

Vascular smooth muscle cells (VSMCs) are constantly exposed to cyclic stretch in the body, which makes it beneficial to study the effects of cyclic stretch on VSMCs. In this study, we developed a poly(dimethyl siloxane) (PDMS) compact six-well device that can be used to study the combined effect of cyclic strain and various growth factors on cultured VSMCs. Cell adhesion, alignment, and proliferation under 10% or 20% cyclic strain at 1 Hz were studied using this surface-enhanced PDMS device. The combined effects of cyclic strain with either transforming growth factor-β, vascular endothelial growth factor, fibroblast growth factor, or epidermal growth factor on VSMC proliferation was also examined. Results showed that VSMCs adhered well on the surface-enhanced multiwell device and they aligned perpendicularly to the direction of the cyclic strain. Cell proliferation was inhibited by 10% cyclic strain at 1 Hz compared with static control. The mitogenic effects of the growth factor were less potent under either 10% or 20% cyclic strain. With simple modification to accommodate more wells, this device could potentially be a useful tool for more economical, high throughput screening application.

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Copyright © 2011 by American Society of Mechanical Engineers
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Figures

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Figure 1

Six-well array device for the study of cell responses under combined effect of cyclic stretch and growth factors: (a) Six-well PDMS membrane with 100 μm diameter for each well. (b) The PDMS device mounted to two holders with one of them fixed and the other connected to a drive shaft through which prescribed cyclic stretches are delivered. (c) The PDMS device placed in the chamber that maintains sterile environment and prevents media evaporation. (d) The chamber was finally connected to the stretching module that delivers prescribed loads.

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Figure 2

The cyclic load in strain applied to the multiwell device at steady state versus time

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Figure 3

Simulation of strain distribution in the multiwell array device. (a) Regional differences in principal strains in a membrane with wells, when the membrane is under 20% strain. (b) Zoom in view of the principal strain distributions at the bottom of a well and in its immediate vicinity.

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Figure 4

Effects of cyclic strain (10% or 20% at 1 Hz) on HASMC proliferation. N=4,  ∗: p<0.05 versus static control at the same time point.

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Figure 5

Cell re-alignment after exposure to cyclic stretch. (a) Microscopic images showing HASMC’s re-alignment in relation to the direction of cyclic stretch after 24 h and 72 h. (b) Histogram showing the angular distribution of cell alignment at 24 h and 72 h for both 10% and 20% stretch cases.

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Figure 6

Effects of growth factors (TGF-β, VEGF, EGF, and FGF) on HASMC proliferation under cyclic stretch (10% or 20% at 1 Hz). N=4,  ∗: p<0.05  ∗∗: p<0.01 versus the same control group without addition of any growth factors

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Figure 7

A 40-Well PDMS device prototype with 100 μm well diameter

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