Article

Annals of Biomedical Engineering

, Volume 32, Issue 11, pp 1461-1470

Cyclic Pressure Affects the Biological Properties of Porcine Aortic Valve Leaflets in a Magnitude and Frequency Dependent Manner

  • Yun XingAffiliated withSchool of Chemical and Biomolecular Engineering, Bioengineering Program, Georgia Institute of Technology
  • , James N. WarnockAffiliated withGeorge W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology
  • , Zhaoming HeAffiliated withWallace H. Coulter School of Biomedical Engineering, Georgia Institute of Technology
  • , Stephen L. HilbertAffiliated withCenter for Devices and Radiological Research (CDRH), Food and Drug Administration
  • , Ajit P. YoganathanAffiliated withSchool of Chemical and Biomolecular Engineering, Bioengineering Program, Georgia Institute of Technology

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Abstract

An understanding of how mechanical forces impact cells within valve leaflets would greatly benefit the development of a tissue-engineered heart valve. Previous studies by this group have shown that exposure to constant static pressure leads to enhanced collagen synthesis in porcine aortic valve leaflets. In this study, the effect of cyclic pressure was evaluated using a custom-designed pressure system. Different pressure magnitudes (100, 140, and 170 mmHg) as well as pulse frequencies (0.5, 1.167, and 2 Hz) were studied. Collagen synthesis, cell proliferation, sGAG synthesis, α-SMC actin expression, and extracellular matrix (ECM) structure were chosen as markers for valvular biological responses. Results showed that aortic valve leaflets responded to cyclic pressure in a magnitude and frequency-dependent manner. Increases in pressure magnitude (with the frequency fixed at 1.167 Hz) resulted in significant increases in both collagen and sGAG synthesis, while DNA synthesis remained unchanged. Responses to pulse frequency (with the magnitude fixed at 100 mmHg) were more complex. Collagen and sGAG synthesis were increased by 25 and 14% respectively at 0.5 Hz; but were not affected at 1.167 and 2 Hz. In contrast, DNA synthesis increased by 72% at 2 Hz, but not at 0.5 and 1.167 Hz. Under extreme pressure conditions (170 mmHg, 2 Hz), collagen and sGAG synthesis were increased but to a lesser degree than at 170 mmHg, and 1.167 Hz. Cell proliferation was not affected. A notable decline in α-SMC actin was observed over the course of the experiments, although no significant difference was observed between the cyclic pressure and control groups. It was concluded that cyclic pressure affected biosynthetic activity of aortic valve leaflets in a magnitude and frequency dependent manner. Collagen and sGAG synthesis were positively correlated and more responsive to pressure magnitude than pulse frequency. DNA synthesis was more responsive to pulse frequency than pressure magnitude. However, when combined, pressure magnitude and pulse frequency appeared to have an attenuating effect on each other. The number of α-SMC actin positive cells did not vary with cyclic pressure, regardless of pulse frequency and pressure magnitude.

Aortic valve leaflets Collagen synthesis Tissue engineering