An in vitro system to simulate and visualize in vivo-like arterial waveforms on cultured endothelial cells

摘要

Arterial endothelial cells are continuously exposed to dynamic, time-varying forces due to the pulsatility of the circulating blood. In vitro models demonstrate these cells to be mechanically responsive and sensitive to the onset rate and magnitude of shear stress as well as time-varying changes in shear [1]. In fact, ECs not only can sense this biomechanical force, but also can discriminate among distinct flow patterns (e.g., steady, oscillatory, turbulent) [1]. Recent efforts have attempted to simulate more realistic in vivo-like flows by imposing aortic pressure waves to an endothelialized tubular model [2]. In this system, however, the effects of pressure and shear stress cannot be decoupled. Additionally, current cell shearing models do not incorporate the complex pulsatile flow patterns that occur in arteries. In an effort to better approximate the actual biomechanical (wall shear stress) stimulus experienced by arterial endothelial cells in vivo and to understand how this stimulus affects endothelial phenotype, we have undertaken the design and fabrication of a novel cone-plate flow system that can be programmed to deliver pulsatile shear stresses in a waveform that mimics that present in different human arterial geometries.