Mechanical stimulation of cell microenvironment for cardiac muscle tissue regeneration: a 3D in-silico model

Abstract

The processes in which cardiac cells are reorganized for tissue regeneration is still unclear. It is a complicated process that is orchestrated by many factors such as mechanical, chemical, thermal, and/or electrical cues. Studying and optimizing these conditions in-vitro is complicated and time costly. In such cases, in-silico numerical simulations can offer a reliable solution to predict and optimize the considered conditions for the cell culture process. For this aim, a 3D novel and enhanced numerical model has been developed to study the effect of the mechanical properties of the extracellular matrix (ECM) as well as the applied external forces in the process of the cell differentiation and proliferation for cardiac muscle tissue regeneration. The model has into account the essential cellular processes such as migration, cell–cell interaction, cell–ECM interaction, differentiation, proliferation and/or apoptosis. It has employed to study the initial stages of cardiac muscle tissue formation within a wide range of ECM stiffness (8–50 kPa). The results show that, after cell culture within a free surface ECM, cells tend to form elongated aggregations in the ECM center. The formation rate, as well as the aggregation morphology, have been found to be a function of the ECM stiffness and the applied external force. Besides, it has been found that the optimum ECM stiffness for cardiovascular tissue regeneration is in the range of 29–39 kPa, combined with the application of a mechanical stimulus equivalent to deformations of 20–25%.