Complex hierarchical organization is a hallmark of tissues and their subsequent integration into organs. A major challenge in tissue engineering is to generate arrays of cells with defined structural organization that display appropriate functional properties. Given what is known about cellular responses to physiochemical cues from the surrounding environment, we can build tissue structures that mimic these microenvironments and validate these platforms using both experimental and computational approaches. Tissue generation encompasses many methods and tissue types, but here we review layering cell sheets to create scaffold-less myocardial patches. We discuss surgical criteria that can drive the design of myocardial cell sheets and the methods used to fabricate, mechanically condition, and functionally test them. We also focus on how computational and experimental approaches could be integrated to optimize tissue mechanical properties by using measurements of biomechanical properties and tissue anisotropy to create predictive computational models. Tissue anisotropy and dynamic mechanical stimuli affect cell phenotype in terms of protein expression and secretion, which in turn, leads to compositional and structural changes that ultimately impact tissue function. Therefore, a combinatorial approach of design, fabrication, testing, and modeling can be carried out iteratively to optimize engineered tissue function.

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Little is known about flow patterns in ventricles supported by continuous flow left ventricular assist devices (LVADs), and valuable information can be obtained with simple flow visualization experiments. We describe the application of several experimental techniques for the in vitro study of ventricular flow patterns (e.g., unsteadiness, vortical motions, stagnation regions) in the presence of a continuous flow LVAD. We used dye streaks, particle paths, and hydrogen bubble techniques to visualize fluid flow in an idealized, static, transparent mock ventricle attached to a Jarvik 2000 continuous flow LVAD. We recorded ventricular flow behavior at various pump speeds while independently adjusting pump flow (by varying the afterload) to emulate in vivo pump flow at various phases of the cardiac cycle. Changes in ventricular flow behavior at different pump flow rates may be of clinical relevance, because continuous flow pumps are extremely sensitive to inflow and outflow pressures and instantaneous pump flow varies significantly at different points throughout the cardiac cycle. Further work is needed to quantitatively compare the flow behavior of different continuous flow devices in a pulsatile ventricular model.

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