Prediction of Stem Cell Differentiation for Cardiac Tissue Engineering Using the Finite Element Method (FEM)

Tissue engineering aims to repair damaged tissues, and to do so it needs three basic elements: cells, scaffolds and signals. Understanding the relationship between these elements, i.e. how the scaffold material and different types of stimuli affect cell behavior, is crucial to form a functional tissue. Mechanotransduction is the transformation of mechanical stimuli into biochemical cues, and many researchers have conducted experiments and created models to better understand how this mechanism works. The Mechanical Bidomain Model (MBM) predicts that mechanotransduction and, therefore, cellular differentiation occur in regions of differences between intra and extracellular displacements. In this work, we applied the MBM to a Matrigel® scaffold seeded with human induced pluripotent stem cells (hiPSCs), and compared the results to a Finite Element (FE) model we developed, considering integrins as rigid bonds between the cell and the scaffold, with an effect similar to a truss link between them. Results showed that both methods suggest a larger difference between displacements (and, therefore, differentiation) on the edge of the cell colonies compared to points closer to the center, which was in accordance with experimental data from the literature. However, in the FE analysis, differentiation should also occur in the vicinity of the center of the colonies, a phenomenon described by Myers et al. (2013), who showed that distinct differentiation strategies can lead to that type of differentiation pattern. In conclusion, the proposed FE model was able to replicate the MBM results, but also predict another type of behavior that was not foreseen before.