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

Abstract

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.

Impact of Oxygen on Pancreatic Islet Survival

“…Oxygen-releasing microspheres were mixed in silicon elastomer (polydimethylsiloxane [PDMS], an O 2 permeable silicone material) to fabricate an O 2 -releasing PDMS-H 2 O 2 disc. 64 Improved insulin secretion was demonstrated by 3D culture using mice β-cells. Although this O 2 generating material is a potent approach, generation of O 2 was gradually lost over the course of the experiment.…”

The emerging field of pancreatic tissue engineering: A systematic review and evidence map of scaffold materials and scaffolding techniques for insulin-secreting cells

“…Whatever method is used for restoration of the islet vasculature, there is a certain formation period to be bypassed. Recent strategies have been either to implant the scaffold at least partially before addition of the cells for pre-vascularization, 25,26,51,92,94,173 or to add oxygen-producing nanoparticles and substrates that ensure survival in the period after implantation when new vasculature has yet been formed 165 (Figure 5(c)). The in vitro treatment of cultured islets prior to implantation with oxygen-generating disks (OxySite; solid encapsulation of calcium peroxide in PDMS disks) proved to have a positive impact on overall graft efficacy by enhancing intra-islet vascularization and decreasing the hypoxic expression of pro-inflammatory cytokines without diminishing the hypoxia inducible factor (HIF)-induced VEGF-A release.…”

“…Increased serum protein absorption, and thus increased cell adhesion to the heparin-coated scaffolds, may be a separate factor leading to vessel ingrowth. 52 In addition to scaffold functionalization with growth-signaling molecules, oxygen-producing materials can further improve islet survival as they decrease irreversible cell damage caused by hypoxia in the initial period after implantation [163][164][165] (Figure 5(c)). Microparticles containing hydrogen peroxide with a functionalized PLGA shell to ensure retarded oxygen release were implanted together with the fibrin-heparin/VEGF scaffold.…”

Large scale and integrated platform for digital mass culture of anchorage dependent cells

“…8a). Because the perforations allowed easy nutrient and oxygen exchange 14 , cells could be cultured in up to five stacks with ~100% cell viability even without medium circulation (Fig. 2c; see Supplementary Fig.…”