Cell Distribution Profiles in Three-Dimensional Scaffolds with Inverted-Colloidal-Crystal Geometry: Modeling and Experimental Investigations

Graphical Abstract

Cell culture strategies: Cell ingrowth in tissue engineering scaffolds is confined to about 200 μm from the surface, due to limitations of nutrient transport. Alternative cell culture strategies, such as seeding only the core of the scaffold (see graphic), are examined and evaluated computationally. After about four days of culture in a direct perfusion reactor, the distribution of cell concentration is highly non-uniform, with bright yellow and dark regions, representing high and low cell densities, respectively.

Abstract

Limited ingrowth of stromal cells is observed when a three-dimensionally ordered scaffold possessing inverted-colloidal-crystal geometry is used to culture adherent cells. In this work, a computational model explaining, as well as predicting, experimental cell distributions is developed. It incorporates a modified Contois cell-growth model that includes the effects of nutrient saturation, competitive product inhibition, and cell-contact inhibition to describe the scaffold–cell system. Our results agree with the hypothesis that the rapid growth of cells on the surface of the scaffold depletes the nutrient supply to the core, resulting in the preferential growth on the exterior of the scaffold. When the cells are cultured in a scaffold subjected to a uniform velocity field, they penetrate to a greater extent into the scaffold core. Alternative seeding and culture strategies are suggested and evaluated.