A multilevel numerical model quantifying cell deformation in encapsulated alginate structures

Abstract

Mechanical forces not only deform cells, but also alter their functions due to biological responses. While current biomanufacturing processes are capable of producing tissue scaffolds with cells encapsulated, it is essential to understand cell responses to process-induced mechanical disturbances. In this study the stresses and deformations of encapsulated cells under compressive loads are quantified via a multilevel nonlinear finite element approach. The macrolevel model is used to mechanically characterize the alginate-cell construct. At the microlevel, the effects of alginate concentration, cell model, and the microlevel geometric heterogeneity on cell deformation are examined. Cells are modeled as single phase inclusions containing only a nucleus phase; then as a two-phase inclusion comprised of a nucleus phase and cytoplasm phase. This study also analyzes the effects of two geometrical parameters-namely, cell size and cell distribution-on the local stress levels of the cell. Subsequent statistical analyses provide insight into the degree of influence of these factors. The study shows that cells embedded in a higher alginate concentration, 3% w/v, experience higher stress levels as compared to cells embedded in a lower alginate concentration, 1.5% w/v. Furthermore, analysis of the geometric heterogeneity indicates that there is a much higher stress concentration in areas where cells are clustered together as compared to areas where cells are relatively isolated.