Cell-Based Modeling of Tissue Developing in the Scaffold Pores of Varying Cross-Sections.

In this work, we present a mathematical model of cell growth in the pores of a perfusion bioreactor through which a nutrient solution is pumped. We have developed a 2-D vertex model that allows us to reproduce the microscopic dynamics of the microenvironment of cells and describe the occupation of the pore space with cells. In this model, each cell is represented by a polygon; the number of vertices and shapes may change over time. The model includes mitotic cell division and intercalation. We study the impact of two factors on cell growth. On the one hand, we consider a channel of variable cross-section, which models a scaffold with a porosity gradient. On the other hand, a cluster of cells grows under the influence of a nutrient solution flow, which establishes a non-uniform distribution of shear stresses in the pore space. We present the results of numerical simulation of the tissue growth in a wavy channel. The model allows us to obtain complete microscopic information that includes the dynamics of intracellular pressure, the local elastic energy, and the characteristics of cell populations. As we showed, in a functional-graded scaffold, the distribution of the shear stresses in the pore space has a complicated structure, which implies the possibility of controlling the growth zones by varying the pore geometry.