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Design Innovation

Design of an Ex Vivo Culture System to Investigate the Effects of Shear Stress on Cardiovascular Tissue

[+] Author and Article Information
Philippe Sucosky

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Parker H. Petit Biotechnology Building, 315 Ferst Drive, Box No. 1, Atlanta, GA 30332-0363philippe.sucosky@bme.gatech.edu

Muralidhar Padala

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Parker H. Petit Biotechnology Building, 315 Ferst Drive, Box No. 1, Atlanta, GA 30332-0363muralidhar.padala@bme.gatech.edu

Adnan Elhammali

School of Physics, Georgia Institute of Technology, Joseph H. Howey Physics Building, 837 State Street, Atlanta, GA 30332-0430gtg139x@mail.gatech.edu

Kartik Balachandran

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Parker H. Petit Biotechnology Building, 315 Ferst Drive, Suite 2116, Atlanta, GA 30332-0363kartik.balachandran@bme.gatech.edu

Hanjoong Jo

Wallace H. Coulter Department of Biomedical Engineering, Emory University, 2005 Woodruff Memorial Building, 1639 Pierce Drive, Atlanta, GA 30322-4600hanjoong.jo@bme.gatech.edu

Ajit P. Yoganathan

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, U.A. Whitaker Building, 313 Ferst Drive, Room 2119, Atlanta, GA 30332-0535ajit.yoganathan@bme.gatech.edu

J Biomech Eng 130(3), 035001 (Apr 22, 2008) (8 pages) doi:10.1115/1.2907753 History: Received January 19, 2007; Revised September 05, 2007; Published April 22, 2008

Mechanical forces are known to affect the biomechanical properties of native and engineered cardiovascular tissue. In particular, shear stress that results from the relative motion of heart valve leaflets with respect to the blood flow is one important component of their mechanical environment in vivo. Although different types of bioreactors have been designed to subject cells to shear stress, devices to expose biological tissue are few. In an effort to address this issue, the aim of this study was to design an ex vivo tissue culture system to characterize the biological response of heart valve leaflets subjected to a well-defined steady or time-varying shear stress environment. The novel apparatus was designed based on a cone-and-plate viscometer. The device characteristics were defined to limit the secondary flow effects inherent to this particular geometry. The determination of the operating conditions producing the desired shear stress profile was streamlined using a computational fluid dynamic (CFD) model validated with laser Doppler velocimetry. The novel ex vivo tissue culture system was validated in terms of its capability to reproduce a desired cone rotation and to maintain sterile conditions. The CFD results demonstrated that a cone angle of 0.5deg, a cone radius of 40mm, and a gap of 0.2mm between the cone apex and the plate could limit radial secondary flow effects. The novel cone-and-plate permits to expose nine tissue specimens to an identical shear stress waveform. The whole setup is capable of accommodating four cone-and-plate systems, thus concomitantly subjecting 36 tissue samples to desired shear stress condition. The innovative design enables the tissue specimens to be flush mounted in the plate in order to limit flow perturbations caused by the tissue thickness. The device is capable of producing shear stress rates of up to 650dyncm2s1 (i.e., maximum shear stress rate experienced by the ventricular surface of an aortic valve leaflet) and was shown to maintain tissue under sterile conditions for 120h. The novel ex vivo tissue culture system constitutes a valuable tool toward elucidating heart valve mechanobiology. Ultimately, this knowledge will permit the production of functional tissue engineered heart valves, and a better understanding of heart valve biology and disease progression.

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Copyright © 2008 by American Society of Mechanical Engineers
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Figures

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Figure 3

Design solution: (a) cross-sectional rendering of the cone-and-plate assembly showing the main components of the system; (b) schematic of the tissue mounting system; and (c) picture of the bottom plate, tissue holders, and plate cover with mounted tissue samples

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Figure 2

(a) Physiologic wall-shear stress waveform experienced by the ventricular surface of aortic valve leaflets over one cardiac cycle and (b) comparison between the initial and corrected cone velocity waveforms used to produce the physiologic ventricular shear stress variations

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Figure 4

Comparison between the physiologic wall-shear stress experienced by the ventricular surface of an aortic valve leaflet, the wall-shear stress predicted by CFD at the center of the area covered by a tissue sample, and the surface-averaged wall-shear stress predicted by CFD over the sample area. The red markers indicate the maximum and minimum wall-shear stress values computed over the sample area.

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Figure 1

Typical cone-and-plate system complying with the dimensional requirements to limit secondary flow effects. The cone located 0.2mm above the flat stationary plate has an angle of 0.5deg and a radius of 40mm. The gap between the cone and the plate is filled with fluid.

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Figure 5

Point-to-point comparison of the tangential velocity measured by LDV and predicted by CFD at three sets of points (r=20mm, r=30mm, and r=36mm, respectively) aligned along the vertical direction, under a steady rotation of the cone (ω=200rpm)

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Figure 6

Comparison between the cone velocity waveform programed into the servo drive and the actual velocity measured on the axis of the servo motor over one period

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Figure 7

DAPI stain on (a) aortic valve leaflet exposed to physiologic ventricular shear stress conditions for 120h and (b) fresh control (nuclei stained in blue)

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