Numerical modeling of oxygen diffusion in tissue spheroids undergoing fusion using function representation and finite volumes.

Abstract

A three-dimensional cell culture called a spheroid serves as a foundational entity in a wide variety of modern tissue engineering applications, including 3D-bioprinting and preclinical drug testing. Lack of oxygen within tissue spheroids hinders metabolism of cells and eventually leads to cell death. Prevention of necrosis is crucial to success of tissue engineering methods and such prevention requires estimation of cell viability in the spheroid. We propose a novel approach for numerical modeling of diffusion in tissue spheroids during their fusion. The approach is based on numerical solutions of partial differential equations and the application of Function Representation (FRep) framework for geometric modeling. We present modeling of oxygen diffusion based on meshes derived from the geometry of fusing spheroids, a method for selecting optimal spheroid size, and several statistics for estimating cellular viability. Our findings provide insights into oxygen diffusion in three-dimensional cell cultures thus improving the robustness of biotechnological methods that employ tissue spheroids.