Design and Computational Validation of a Novel Bioreactor for Conditioning Vascular Tissue to Time-Varying Multidirectional Fluid Shear Stress

Purpose The cardiovascular endothelium experiences pulsatile and multidirectional fluid wall shear stress (WSS). While the effects of non-physiologic WSS magnitude and pulsatility on cardiovascular function have been studied extensively, the impact of directional abnormalities remains unknown due to the challenge to replicate this characteristic in vitro. To address this gap, this study aimed at designing a bioreactor capable of subjecting cardiovascular tissue to time-varying WSS magnitude and directionality. Methods The device consisted of a modified cone-and-plate bioreactor. The cone rotation generates a fluid flow subjecting tissue to desired WSS magnitude, while WSS directionality is achieved by altering the alignment of the tissue relative to the flow at each instant of time. Computational fluid dynamics was used to verify the device ability to replicate the native WSS of the proximal aorta. Cone and tissue mount velocities were determined using an iterative optimization procedure. Results Using conditions derived from cone-and-plate theory, the initial simulations yielded root-mean-square errors of 22.8 and 8.4% in WSS magnitude and angle, respectively, between the predicted and the target signals over one cycle, relative to the time-averaged target values. The conditions obtained after two optimization iterations reduced those errors to 3.5 and 0.5%, respectively, and generated 0.2% and 0.01% difference in time-averaged WSS magnitude and angle, respectively, relative to the target waveforms. Conclusions A bioreactor capable of generating simultaneously desired time-varying WSS magnitude and directionality was designed and validated computationally. The ability to subject tissue to in vivo-like WSS will provide new insights into cardiovascular mechanobiology and disease.