Development and characterization of a novel microfluidic bioreactor system utilized for examining hemodynamic effects on cellular response

Abstract

Understanding the contribution of individual mechanical stimuli to cardiovascular pathogenesis is critically important for understanding and treating cardiovascular disease, and microfluidic bioreactors are a useful tool for these studies. Cardiovascular bioreactors are uniquely complex because they require the simultaneous application of fluid shear stress and dynamic strain. One of the key shortcomings of current mechanotransduction bioreactors that we wanted to address in this thesis was the effect of dynamic strain on the fluid shear conditions in a bioreactor system. In this thesis, we designed, developed and validated a microfluidic bioreactor system which can accurately recapitulate the major hemodynamic mechanical parameters of shear stress and strain. We characterized the system using computational modeling and validated computational models by developing novel three dimensional particle velocimetry (PIV) techniques. Computational modeling of the microfluidic bioreactor during dynamic strain demonstrated that shear stress experience by cells in a bioreactor is altered by applying dynamic strain. The PIV methods developed allowed us to visualize the three dimensional fluid velocity profile in the bioreactor during dynamic strain and allowed us to measure and validate the computational models of bioreactor dynamics. In addition, we applied this system to investigate the effects of mechanical stimuli on omental mesothelium.