Effect of Fibrotic Layer Formation on Oxygen Delivery to Pancreatic Cells in a (REDACTED) Cell Encapsulation Device

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Fibrosis is an immune response that handicaps the effectiveness of biomedical devices for individuals with type 1 diabetes. As an implant becomes encapsulated with connective tissue, forming a fibrotic layer, cells within a device may be unable to survive, leading to reduced performance. Recent studies have focused on fibrosis and its impact on insulin producing cells, but little research has explored the role fibrosis plays with regards to oxygen transfer. Oxygen transfer into a pancreatic cell encapsulation device was explored in this study. Specifically, this device contains (redacted) surrounded by an alginate hydrogel with cells. When implanted, a fibrotic layer forms around the device; in this study, various thicknesses, compositions, and percent coverages of this layer were analyzed to observe their impact on survivability of cells due to limited oxygen availability. In this study, oxygen transfer was explored within a (redacted) biomedical device with varying fibrotic layer thicknesses and percentages in order to observe the survival rate of insulin-producing cells within a hydrogel layer. The device used in this study contains an internal alginate hydrogel layer surrounded by a layer of fibrosis. The models were all built using COMSOL MultiphysicsⓇ Modeling Software and make use of oxygen diffusion from an external boundary condition and oxygen consumption based on Michaelis-Menten Kinetics. Under the 1D model, device oxygen levels were studied under varying severity of the fibrotic response and in several oxygen environments. Parameters including fibrotic layer thickness, seeding density within the hydrogel layer, and boundary oxygen concentration under full fibrotic layer coverage were varied. Results indicated that a higher seeding density results in lower concentration gradients, as more cells are present in the hydrogel and consuming more oxygen. Similarly, a thicker fibrotic layer results in less oxygen entering the hydrogel layer. Under the 3D model, the effects of various percentages and thickness of the fibrotic layer were studied, with coverages varying in intervals of 25%. In the scenario of 100% fibrotic layer coverage at 200μm thickness, the model indicates most cells in the hydrogel become necrotic due to the limited oxygen and high oxygen consumption from the fibrotic layer. Under a more idealized situation with 25% coverage of fibrotic tissue at 10μm thickness, oxygen concentration is still depleted but less egregiously, with little risk of necrosis. The sensitivity analysis indicates how the model is more sensitive to subtle changes in seeding density and surface oxygen concentration, as opposed to other parameters. Data obtained in the study was validated via comparisons with oxygen concentrations within the fibrotic layer from another existing 1D analytical model. Similarly, oxygen concentration in the hydrogel region of the 3D model was compared to data obtained from another study measuring oxygen concentration within a device encapsulated by fibrosis. Overall, the results emphasize the importance in eliminating any possible fibrotic encapsulation around a biomedical device.

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Alginate hydrogel, Diabetes, Fibrosis, Encapsulated Cells, COMSOL Multiphysics


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