Design and validation of a novel bioreactor to subject aortic valve leaflets to side-specific shear stress

Hemodynamic stresses are presumed to play an important role in the development of calcific aortic valve disease (CAVD). The elucidation of the shear stress mechanisms involved in the pathogenesis of CAVD has been hampered by the complexity of the native unsteady and side-specific valvular flow environment. To address this gap, this article describes the design and validation of a novel device to expose leaflet samples to time-dependent side-specific shear stress. The device built on a double cone-and-plate geometry was dimensioned based on our previous single-sided shear stress device that minimizes secondary flow effects inherent to this geometry. A fluid-structure interaction (FSI) model was designed to predict the actual shear stress produced on a tissue sample mounted in the new device. Staining was performed on porcine leaflets conditioned in the new bioreactor to assess endothelial integrity and cellular apoptosis. The FSI results demonstrated good agreement between the target (native) and the actual side-specific shear stress produced on a tissue sample. No significant difference in endothelial integrity and cellular apoptosis was detected between samples conditioned for 96 h and fresh controls. This new device will enable the investigation of valvular response to normal and pathologic hemodynamics and the potential mechano-etiology of CAVD.