Adaptive Discontinuous Galerkin Finite Element Methods for a Diffuse Interface Model of Biological Growth

This PhD dissertation concentrates on the development and application of adaptive Discontinuous Galerkin Finite Element (DG-FE) methods for the numerical solution of a Cahn-Hilliard-type diffuse interface model for biological growth. Models of this type have become popular for studying cancerous tumor progression in vivo. The work in this dissertation advances the state-of-the-art in the following ways: To our knowledge the work here contains the first primitive-variable, completely discontinuous numerical implementations of a 2D scheme for the Cahn-Hilliard equation as well as a diffuse interface model of cancer growth. We provide numerical evidence that the schemes above are convergent, with the optimal order. The efficiency of the numerical algorithms depends largely on the implementation of fast solvers for the systems of equations resulting from the DG-FE discretizations. We have developed such capabilities based on multigrid and sparse direct solver techniques. We demonstrate proof-of-concept regarding the implementation of a practical spatially adaptive meshing algorithm for the numerical schemes just mentioned and th1 effective use of a very simple, but powerful, marking strategy based on an inverse estimate. We demonstrate proof-of-concept for a novel simplified diffuse interface model of tumor growth. This model is essentially the Cahn-Hilliard equation with an added source term that is specialized for the context of cancerous tumor progression. We devise and analyze a mixed DG-FE scheme of convex splitting (CS) type for the Cahn-Hilliard equation in any space dimension. Specifically, we prove that our scheme is unconditionally energy stable and unconditionally uniquely solvable. Likewise, we devise and analyze a CS, mixed DG-FE scheme for our diffuse interface cancer model. This scheme is energy stable for any (positive) time step size and for any (positive) space step size that is sufficiently small

A discontinuous Galerkin method for unsteady two-dimensional convective flows

We develop a High-Order Symmetric Interior Penalty (SIP) Discontinuous Galerkin (DG) Finite Element Method (FEM) to investigate two-dimensional in space natural convective flows in a vertical cavity. The physical problem is modeled by a coupled nonlinear system of partial differential equations and admits various solutions including stable and unstable modes in the form of traveling and/or standing waves, depending on the governing parameters. These flows are characterized by steep boundary and internal layers which evolve with time and can be well-resolved by high-order methods that also are adept to adaptive meshing. The standard no-slip boundary conditions which apply on the lateral walls, and the periodic conditions prescribed on the upper and lower boundaries, present additional challenges. The numerical scheme proposed herein is shown to successfully address these issues and furthermore, large Prandtl number values can be handled naturally. Discontinuous source terms and coefficients are an innate feature of multiphase flows involving heterogeneous fluids and will be a topic of subsequent work. Spatially adaptive Discontinuous Galerkin Finite Elements are especially suited to such problems

Computational Modelling of Tissue-Engineered Cartilage Constructs

Cartilage is a fundamental tissue to ensure proper motion between bones and damping of mechanical loads. This tissue often suffers damage and has limited healing capacity due to its avascularity. In order to replace surgery and replacement of joints by metal implants, tissue engineered cartilage is seen as an attractive alternative. These tissues are obtained by seeding chondrocytes or mesenchymal stem cells in scaffolds and are given certain stimuli to improve establishment of mechanical properties similar to the native cartilage. However, tissues with ideal mechanical properties were not obtained yet. Computational models of tissue engineered cartilage growth and remodelling are invaluable to interpret and predict the effects of experimental designs. The current model contribution in the field will be presented in this chapter, with a focus on the response to mechanical stimulation, and the development of fully coupled modelling approaches incorporating simultaneously solute transport and uptake, cell growth, production of extracellular matrix and remodelling of mechanical properties.publishe

Evaluation of Diffusive Transport and Cellular Uptake of Nutrients in Tissue Engineered Constructs Using a Hybrid Discrete Mathematical Model

Tissue engineering systems for orthopedic tissues, such as articular cartilage, are often based on the use of biomaterial scaffolds that are seeded with cells and supplied with nutrients or growth factors. In such systems, relationships between the functional outcomes of the engineered tissue construct and aspects of the initial system design are not well known, suggesting the use of mathematical models as an additional tool for optimal system design. This study develops a reaction-diffusion model that quantitatively describes the competing effects of nutrient diffusion and the cellular uptake of nutrients in a closed bioreactor system consisting of a cell-seeded scaffold adjacent to a nutrient-rich bath. An off-lattice hybrid discrete modeling framework is employed in which the diffusion equation incorporates a loss term that accounts for absorption due to nutrient uptake by cells that are modeled individually. Numerical solutions are developed based on a discontinuous Galerkin finite element method with high order quadrature to accurately resolve fine-scale cellular effects. The resulting model is applied to demonstrate that the ability of cells to absorb nutrients over time is highly dependent on both the normal distance to the nutrient bath, as well as the nutrient uptake rate for individual cells