Design and Validation of a Novel Bioreactor to Expose Aortic Valve Leaflets to Side-Specific Shear Stress

Calcific aortic valve disease (CAVD), the most common aortic valve disorder, is characterized by an accumulation of calcium on the valve leaflets that contributes to the obstruction of the left ventricular outflow and progressive heart failure. CAVD follows an active process presumably triggered by atherogenic risk factors and hemodynamic cues^1,2. Resulting from the relative motion between the deforming leaflets and the surrounding blood flow, fluid shear stress is an important component of the valve hemodynamic environment. The ventricular surface of the leaflets is exposed to a unidirectional pulsatile shear stress, while the aortic surface experiences a bidirectional oscillatory shear stress³. The characterization of the effects of shear stress on valvular pathogenesis, which requires the replication of the native valvular shear stress in the laboratory setting, has been hampered by this hemodynamic complexity. In an effort to address this challenge, the goal of this study was to design and validate a novel apparatus capable of exposing simultaneously but independently both surfaces of aortic valve leaflets to native side-specific shear stress. The device based on a cone-and-plate geometry was validated with respect to its ability to expose each surface of aortic valve leaflets to its native, time-varying shear stress waveform, while maintaining the tissue under sterile conditions for 96 hours.