Overcoming conventional modeling limitations using image- driven lattice-boltzmann method simulations for biophysical applications

The challenges involved in modeling biological systems are significant and push the boundaries of conventional modeling. This is because biological systems are distinctly complex, and their emergent properties are results of the interplay of numerous components/processes. Unfortunately, conventional modeling approaches are often limited by their inability to capture all these complexities. By using in vivo data derived from biomedical imaging, image-based modeling is able to overcome this limitation. In this work, a combination of imaging data with the Lattice-Boltzmann Method for computational fluid dynamics (CFD) is applied to tissue engineering and thrombogenesis. Using this approach, some of the unanswered questions in both application areas are resolved. In the first application, numerical differences between two types of boundary conditions: “wall boundary condition” (WBC) and “periodic boundary condition” (PBC), which are commonly utilized for approximating shear stresses in tissue engineering scaffold simulations is investigated. Surface stresses in 3D scaffold reconstructions, obtained from high resolution microcomputed tomography images are calculated for both boundary condition types and compared with the actual whole scaffold values via image-based CFD simulations. It is found that, both boundary conditions follow the same spatial surface stress patterns as the whole scaffold simulations. However, they under-predict the absolute stress values approximately by a factor of two. Moreover, it is found that the error grows with higher scaffold porosity. Additionally, it is found that the PBC always resulted in a lower error than the WBC. In a second tissue engineering study, the dependence of culture time on the distribution and magnitude of fluid shear in tissue scaffolds cultured under flow perfusion is investigated. In the study, constructs are destructively evaluated with assays for cellularity and calcium deposition, imaged using µCT and reconstructed for CFD simulations. It is found that both the shear stress distributions within scaffolds consistently increase with culture time and correlate with increasing levels of mineralized tissues within the scaffold constructs as seen in calcium deposition data and µCT reconstructions. In the thrombogenesis application, detailed analysis of time lapse microscopy images showing yielding of thrombi in live mouse microvasculature is performed. Using these images, image-based CFD modeling is performed to calculate the fluid-induced shear stresses imposed on the thrombi’s surfaces by the surrounding blood flow. From the results, estimates of the yield stress (A critical parameter for quantifying the extent to which thrombi material can resist deformation and breakage) are obtained for different blood vessels. Further, it is shown that the yielding observed in thrombi occurs mostly in the outer shell region while the inner core remains intact. This suggests that the core material is different from the shell. To that end, we propose an alternative mechanism of thrombogenesis which could help explain this difference. Overall, the findings from this work reveal that image-based modeling is a versatile approach which can be applied to different biomedical application areas while overcoming the difficulties associated with conventional modeling

Fluid flow in a Porous Scaffold for Microtia by Lattice Boltzmann Method

The birth deformity of ear, known as microtia, varies from a minimal deformed ear to the absence of auricular tissue or anotia. This malformation has been treated by reconstructing the external ear, mainly by autogenous rib cartilage in auricular repair. The fabrication of the ear framework is a prolonged reconstructive procedure and depends of the surgeon’s skill. In order to avoid these inconveniences and reduce surgery time, it was proposed in a previous work to use implants made with biocompatible materials. One of these is a scaffold made by fused deposition modeling using PLA based in the three-dimensional geometry of the ear cartilage. The aim of this work is to evaluate the feasibility of this scaffold to perform cell culture in a perfusion biorreactor by estimating the flow transport characteristics in porous media using a scaffold with the porous geometry of the human auricular cartilage for microtia. Flow and heat transfer through the scaffold were simulated by the lattice Boltzmann method, and permeability and shear stress distribution were obtained at different Reynolds numbers. The permeability values of the scaffold achieved are in the order of magnitude of scaffolds used for cell culture. Linear dependencies between maximum shear stress and Reynolds number, and between maximum shear stress and permeability were obtained. The values of shear stress achieved correspond to high percentage of cell viability. The scaffolds for microtia treatment with the proposed filling pattern select is appropriate for cell culture in a perfusion bioreactor with characteristics similar to those described herein

Micro-computed tomography pore-scale study of flow in porous media: Effect of voxel resolution

A fundamental understanding of flow in porous media at the pore-scale is necessary to be able to upscale average displacement processes from core to reservoir scale. The study of fluid flow in porous media at the pore-scale consists of two key procedures: Imaging - reconstruction of three-dimensional (3D) pore space images; and modelling such as with single and two-phase flow simulations with Lattice-Boltzmann (LB) or Pore-Network (PN) Modelling. Here we analyse pore-scale results to predict petrophysical properties such as porosity, single-phase permeability and multi-phase properties at different length scales. The fundamental issue is to understand the image resolution dependency of transport properties, in order to up-scale the flow physics from pore to core scale. In this work, we use a high resolution micro-computed tomography (micro-CT) scanner to image and reconstruct three dimensional pore-scale images of five sandstones (Bentheimer, Berea, Clashach, Doddington and Stainton) and five complex carbonates (Ketton, Estaillades, Middle Eastern sample 3, Middle Eastern sample 5 and Indiana Limestone 1) at four different voxel resolutions (4.4 µm, 6.2 µm, 8.3 µm and 10.2 µm), scanning the same physical field of view. Implementing three phase segmentation (macro-pore phase, intermediate phase and grain phase) on pore-scale images helps to understand the importance of connected macro-porosity in the fluid flow for the samples studied. We then compute the petrophysical properties for all the samples using PN and LB simulations in order to study the influence of voxel resolution on petrophysical properties. We then introduce a numerical coarsening scheme which is used to coarsen a high voxel resolution image (4.4 µm) to lower resolutions (6.2 µm, 8.3 µm and 10.2 µm) and study the impact of coarsening data on macroscopic and multi-phase properties. Numerical coarsening of high resolution data is found to be superior to using a lower resolution scan because it avoids the problem of partial volume effects and reduces the scaling effect by preserving the pore-space properties influencing the transport properties. This is evidently compared in this study by predicting several pore network properties such as number of pores and throats, average pore and throat radius and coordination number for both scan based analysis and numerical coarsened data

Computational Fluid Dynamics for Modeling and Simulation of Intraocular Drug Delivery and Wall Shear Stress in Pulsatile Flow

Indiana University-Purdue University Indianapolis (IUPUI)The thesis includes two application studies of computational fluid dynamics. The first is new and efficient drug delivery to the posterior part of the eye, a growing health necessity worldwide. Current treatment of eye diseases, such as age-related macular degeneration (AMD), relies on repeated intravitreal injections of drug-containing solutions. Such a drug delivery has significant cant drawbacks, including short drug life, vital medical service, and high medical costs. In this study, we explore a new approach of controlled drug delivery by introducing unique porous implants. Computational modeling contains physiological and anatomical traits. We simulate the IgG1 Fab drug delivery to the posterior eye to evaluate the effectiveness of the porous implants to control the drug delivery. The computational model was validated by established computation results from independent studies and experimental data. Overall, the results indicate that therapeutic drug levels in the posterior eye are sustained for eight weeks, similar to those performed with intravitreal injection of the same drug. We evaluate the effects of the porous implant on the time evaluation of the drug concentrations in the sclera, choroid, and retina layers of the eye. Subsequent simulations were carried out with varying porosity values of a porous episcleral implant. Our computational results reveal that the time evolution of drug concentration is distinctively correlated to drug source location and pore size. The response of this porous implant for controlled drug delivery applications was examined. A correlation between porosity and fluid properties for the porous implants was revealed in this study. The second application lays in the computational modeling of the oscillatin

Multiphysics modeling for bone remodeling simulation: A methodological framework

In the present study an object oriented integrative modeling methodology is proposed for the construction of synthetic, computational models of bone-bone environment system that allow its simulation under in vivo conditions. The analytical mathematical approach to model and study ordinary materials will be outlined, indicating its limitations when dealing with biomaterials in physiological environments. The proposed object oriented integrative modeling will be explained emphasizing its advantages and possibilities. Finally, the architecture of the "in vivo" modeling and simulation software framework is shown, described and explained indicating further work based on this framework