A novel physiological strain rate bioreactor for engineered heart valve mechanobiology

Heart valve leaflets undergo dramatic accelerations during opening and closing, exposing leaflet tissues not only to large flexural and tensile deformations, but also at high deformation rates. Thus, the homeostatic mechanical state of the resident valvular interstitial cells comprises rapid rates of cyclic deformation in the context of time varying extracellular matrix apparent stiffnesses. To date, the effects of such factors on the phenotype of valvular interstitial cells and other clinically-relevant cell sources have yet to be fully elucidated. In particular, previous cyclic flexure and tension bioreactors were capable of producing physiological loading frequencies (e.g., 1 Hz), however the maximum rates of displacement were limited by the screw driven mechanism of linear actuation. Here we describe for the first time a novel bioreactor capable of applying cyclic flexural and tensile deformations to engineered heart valve tissues at physiological strain rates (i.e., exceeding ~1000%/s). The bioreactor is expected to contribute to developing conditioning regimens for engineered heart valve tissues.