Date of Graduation

5-2014

Document Type

Thesis

Degree Name

Bachelor of Science in Biomedical Engineering

Degree Level

Undergraduate

Department

Biomedical Engineering

Advisor/Mentor

Jin, Sha

Committee Member/Reader

Muldoon, Timothy J.

Committee Member/Second Reader

Kim, Myunghee M.

Abstract

Introduction: Diabetes affects millions of people and its prevalence is increasing by 2-5% per year. A promising method for the control of diabetes is the transplant of pancreatic β-cell mass. Unfortunately, there is a shortage of the donor tissue that is needed to replace β-cell mass. A potential source of β-cells is the production of β-cells in vitro, but the proliferation rate of β-cells is very slow and elevating the proliferation rate can result in loss of cell function. We observed that β-cells benefit from being cultured in a 3D environment, but in the 3D culture the β-cells often die due to hypoxic conditions. The goal of this work is to evaluate the utility of an oxygenation-aided 3D β-cell culture system for producing biological functional β-cells using mathematical modeling. Methods: In this study, we established a mathematical model to calculate the oxygen-release capacity of an oxygenator that is made of hydrogen peroxide (H2O2) encapsulated in polydimethlysiloxane (PDMS). We then developed a simulation using COMSOL Multiphysics software to model the changes in oxygen concentration inside an oxygenator embedded β-cell-collagen scaffold culture. The software was also used to design cell culture experiments that aim to provide the cells with sufficient oxygen to avoid hypoxic conditions deep inside a 3D scaffold. Results: Our experiments demonstrated that oxygen is gradually released from the oxygenator for at least two weeks. Using the COMSOL Multiphysics software, we were able to estimate the distribution of oxygen in a culture system. The simulations showed that the oxygenator was able to increase (but not fully oxygenate) the levels of oxygen within a cell culture of 1 million beta cells, but different cell-oxygenator configurations could fully oxygenate the culture. Discussion: Using the simulations it was found that the addition of the oxygenator to a 3D β-cell-collagen scaffold culture improved the hypoxic conditions of the cell culture, but one oxygenator disk was not sufficient to fully oxygenate the culture. However, we found that culture conditions could be adjusted to optimize the culture conditions for β-cell growth.

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