Abstract 12608: Design and Fabrication of a Working Tissue Model of the Developing Embryonic Heart

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Introduction: Currently, there are no in vitro models that fully recapitulate cardiogenesis. Knowledge gained by a three-dimensional model of cardiogenesis could be useful to improve techniques to engineer heart tissue or to act as a model of the onset of congenital heart defects. Within this study, we designed a tissue engineered model of the embryonic heart tube that undergoes the looping phenomenon. Methods: Embryonic heart tubes (EHT) were engineered using a novel casting method (Figure 1A, B). Tubes were created through serial castings resulting in an inner acellular layer surrounded by a thin iPS derived cardiomyocyte layer, mimicking the in vivo cross-sectional anatomy. In the developing heart, looping is driven through both internal and external forces, leading to elongation of the tube resulting in a rightward rotation at the cranial end of the embryo and a dorsal deflection at the caudal end. To mimic this, we designed a bioreactor system (Figure 1C) that would enable 180°rotation on the “cranial end”, 300% dorsal deflection on the “caudal end”, shortening by 100% for the entire tissue. Results: EHTs were maintained for seven days via perfusion culture (Figure 1D). Histologic analysis confirmed cross-sectional orientation that matches the native heart tube at day 22 (Figure 1B). EHTs were found to remain patency, perfusability and viability during culture (Figure 1E). When exposed to external forces within the bioreactor, tubes looped similarly to what is seen during cardiogenesis with both ends fusing together into a primitive four-chambered shape (Figure 1D, F; numbers indicate location within the tissue the image was taken), including potential ventricular septal formation (white arrow). Conclusions: We successfully engineered a heart tube model that mimics the cross-sectional anatomy and looping of the embryonic heart tube. This model could be further expanded to further study cardiogenesis or modified to study the onset of congenital heart defects.