Generating in-silico Models of Engineered Heart Tissues: The Importance of Using Length-Dependent Activation

Engineered heart tissues (EHTs) are a promising technology to improve cardiac disease treatment. However, manufacturing EHTs with mature iPSC-CMs remains a challenge due to, in part, our lack of understanding of the mechanobiology of these tissues. Developing computational models can help elucidate the complex interplay between the extracellular matrix, the boundary conditions, and the myofibril development in EHTs. In order to accurately represent EHT mechanics, it is necessary to understand what biophysical properties are relevant. In this study, we focus on studying the impact of the length-dependent activation (LDA) property in EHTs, which is known to be crucial in whole heart mechanics. Using a biomechanical computational model, we show that when LDA is considered, the simulated displacements are more accurate, and the stretches are more spatially homogeneous. Furthermore, the LDA modifies how different parameters impact the tissue’s mechanical performance, and it is, therefore, crucial to EHT modeling.