Abstract 3548: Large 3-Dimensional Tissue Engineered Cardiac Patch With Controlled Electrical Anisotropy
The tissue engineered cardiac patch holds promise for the repair of damaged heart. However, methods to control the direction and degree of 3D cardiac cell alignment in large tissue constructs are lacking. Here, for the first time, we describe a versatile and reproducible method to control structural and functional anisotropy of large cardiac constructs. A mixture of neonatal rat cardiomyocytes and fibrin gel was injected into microfabricated polydimethylsiloxane molds containing an array of staggered, 0.8 mm spaced, 0.2 mm wide, and 1.5 mm tall hexagonal posts. These posts created elliptical pores that facilitated diffusion of oxygen and nutrients to embedded cells, allowing the formation of large (2 cm2), highly viable and cellular 3D tissue constructs. Systematic increase in the post length (0.6, 1.2, and 2 mm) imposed higher local strains on the cells yielding more compacted tissue bundles (bundle width 0.743±0.028, 0.507±0.037 and 0.426±0.031 mm) and increased overall cell alignment (deviation angle 33.6±1.5o, 26.2±1.9o and 19.8±0.9o) (Fig. A1– 6⇓). The increase in alignment increased velocity anisotropy ratio of 3D electrical conduction (1.21±0.08, 1.54±0.12 and 1.76±0.19) (Fig. B⇓). The maximum longitudinal velocity of 32 cm/s in tissue constructs was similar to that of anisotropic 2D monolayers suggesting a high degree of 3D cell coupling in constructs. Importantly, no reentrant arrhythmias were induced by rapid pacing revealing the protective source-load geometry of elliptical pores. We conclude that this novel method enables reliable production of cardiac tissues with anisotropic structure and function that can be tailored for various therapeutic applications.