Improvements to the bioartificial pancreas: characterizing an encapsulation material and studying the effects of hypoxia on islet functions

Abstract

Diabetes is a metabolic disease in which a person has high blood sugar resulting from one of two ways: the pancreas not producing enough insulin to maintain normal blood sugar levels or insulin resistance. It is a major health problem that affects approximately 23.6 million people in the United States, 27% of which (about 6.4 million people) have become insulin-dependent. Without proper regulation, deviations from normoglycemia increases risk for heart disease, kidney failure, blindness, and nerve damage. To further understand how to improve bioartificial pancreas development, this thesis focuses on two aims: 1) characterizing PEGylated beads by stability and insulin diffusivity in order to refine the encapsulation material and 2) determining the effects of oxygen availability on the function of encapsulated adult porcine and neonatal porcince islets. For the first aim, the paper hypothesizes that PEGylating, or covalently binding poly(ethylene glycol) [PEG], the AP hydrogels will help reduce the fibrotic adhesion due to the steric hindrance effects of the PEG compound. In order to prevent fibrotic overgrowth, the PEG layer must be stable. However, to achieve the main goal of the bioartificial pancreas, the PEG layer should not affect the insulin diffusivity compared with AP capsules. The second aim studied the effects of oxygen availability on encapsulated islets to enhance our understanding of the functions of islets under hypoxic conditions. This experiment will look at total protein content as a relationship to protein synthesis, the ratio of insulin secretion to intracellular insulin content, and metabolic activity of encapsulated cells exposed to different oxygen levels.