Modeling spatial distribution of oxygen in 3d culture of islet beta‐cells

Three‐dimensional (3D) scaffold culture of pancreatic β‐cell has been proven to be able to better mimic physiological conditions in the body. However, one critical issue with culturing pancreatic β‐cells is that β‐cells consume large amounts of oxygen, and hence insufficient oxygen supply in the culture leads to loss of β‐cell mass and functions. This becomes more significant when cells are cultured in a 3D scaffold. In this study, in order to understand the effect of oxygen tension inside a cell‐laden collagen culture on β‐cell proliferation, a culture model with encapsulation of an oxygen‐generator was established. The oxygen‐generator was made by embedding hydrogen peroxide into nontoxic polydimethylsiloxane to avoid the toxicity of a chemical reaction in the β‐cell culture. To examine the effectiveness of the oxygenation enabled 3D culture, the spatial‐temporal distribution of oxygen tension inside a scaffold was evaluated by a mathematical modeling approach. Our simulation results indicated that an oxygenation‐aided 3D culture would augment the oxygen supply required for the β‐cells. Furthermore, we identified that cell seeding density and the capacity of the oxygenator are two critical parameters in the optimization of the culture. Notably, cell‐laden scaffold cultures with an in situ oxygen supply significantly improved the β‐cells' biological function. These β‐cells possess high insulin secretion capacity. The results obtained in this work would provide valuable information for optimizing and encouraging functional β‐cell cultures. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:221–228, 2017