Toward Hierarchical Assembly of Aligned Cell Sheets into a Conical Cardiac Ventricle Using Microfabricated Elastomers.

Despite current efforts in organ-on-chip engineering to construct miniature cardiac models, they often lack some physiological aspects of the heart, including fiber orientation. This motivates the development of bioartificial left ventricle models that mimic the myofiber orientation of the native ventricle. Herein, an approach relying on microfabricated elastomers that enables hierarchical assembly of 2D aligned cell sheets into a functional conical cardiac ventricle is described. Soft lithography and injection molding techniques are used to fabricate micro-grooves on an elastomeric polymer scaffold with three different orientations ranging from -60° to +60°, each on a separate trapezoidal construct. The width of the micro-grooves is optimized to direct the majority of cells along the groove direction and while periodic breaks are used to promote cell-cell contact. The scaffold is wrapped around a central mandrel to obtain a conical-shaped left ventricle model inspired by the size of a human left ventricle 19 weeks post-gestation. Rectangular micro-scale holes are incorporated to alleviate oxygen diffusional limitations within the 3D scaffold. Cardiomyocytes within the 3D left ventricle constructs showed high viability in all layers after 7 days of cultivation. The hierarchically assembled left ventricle also provided functional readouts such as calcium transients and ejection fraction.