(E-190) Development of an engineered cardiac tissue chip to subject recellularized porcine myocardial tissue slices to biomechanical loading

Introduction:: Engineered Cardiac Tissue Chips (CTCs) can be a potentially transformative model to study the mechanisms of cardiovascular disease and for drug discovery and toxicity testing. CTC can better serve this purpose if they are structurally and functionally similar to the native heart. Tissue remodeling is a common condition associated with altered hemodynamic loading and unloading that ultimately leads to heart failure. Our study is focused on creating engineered tissue where decellularized porcine myocardial tissue is recellularized and subject to biomechanical loading associated with pathological hemodynamic stress.

Materials and Methods:: Porcine myocardium was cut into 380 µm slices using a vibrating microtome. The resulting slices were cut out into an obround shape (13 mm long and 5mm wide) with the help of a custom-built tissue punch and restrained into the culture chamber of CTC with the help of PDMS posts (1 mm diameter). The tissues were decellularized using a detergent and subsequently recellularized with H9c2 cells. Recellularized porcine myocardial slide was subject to biomechanical loading within a flow loop that enables pressure-volume changes associated with the left ventricle.

Results, Conclusions, and Discussions:: Using this approach, we successfully recellularized decellularized porcine myocardial slices at appropriate cell densities, integrated the recellularized slices within the CTC tissue culture chamber and subject the recellularized tissues to pressure-volume changes associated with pressure overload. We are in the process of quantifying structural and functional changes as a consequence of pathological hemodynamic stresses associated with pressure overload

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