Contributions of a Finite Element Model for the Geometric Optimization of an Implantable Bioartificial Pancreas

Dulong, Jean-Luc; Legallais, Cécile

doi:10.1046/j.1525-1594.2002.07080.x

Cited by 16 publications

(7 citation statements)

References 25 publications

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“…This per volume value is similar to that used by Avgoustiniatos and co-workers (0.034 mol/s/m 3 [ 44 ]; 0.050 mol/s/m 3 [ 23 ]) and Tilakaratne and co-workers (0.046 mol/s/m 3 ) [ 29 ]. As a per islet value (0.06 × 10 -12 mol·s -1 /islet), it is similar to that assumed by Dulong and Legallais (0.063 × 10 -12 mol·s -1 /islet) [ 30 , 42 ]; somewhat less than that assumed by Papas, Avgoustiniatos, and co-workers (0.127 × 10 -12 mol·s -1 /islet [ 20 , 32 ]; 0.074 × 10 -12 mol·s -1 /islet [ 43 ]); and slightly larger than those measured recently in various settings by Sweet and co-workers (e.g., 0.025–0.048 × 10 -12 mol·s -1 /islet at 3 mM basal- or 20 mM high glucose [ 45 , 46 ]). Converted to a per cell value (3.0 × 10 -17 mol·s -1 /cell), it is also in general agreement with values observed with other high-demand cells [ 21 ].…”

Section: Discussionsupporting

confidence: 82%

“…A maximum oxygen consumption rate R max (per unit islet volume) of 0.034 mol·s -1 ·m -3 was used in all calculations. With a standard islet of 150 μ m diameter (and islet equivalent IEQ volume V IEQ of 1.77 × 10 -12 m 3 ), this corresponds to a consumption rate (per islet) of R max = 0.06 × 10 -12 mol·s -1 /islet; both values being in the range of those measured and used in various works [ 20 , 23 , 29 , 30 , 32 , 42 - 46 ]. As Michaelis-Menten constant, = 1.0 × 10 -3 mol·m -3 (1 μ M) was assumed, corresponding to = 0.7 mmHg – similar to the frequently used 0.44 mmHg value [ 23 , 27 , 29 , 32 ] or even to that determined originally for mitochondria [ 39 ].…”

Section: Methodsmentioning

confidence: 96%

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FEM-based oxygen consumption and cell viability models for avascular pancreatic islets

Buchwald

2009

Theor Biol Med Model

157

177

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Background: The function and viability of cultured, transplanted, or encapsulated pancreatic islets is often limited by hypoxia because these islets have lost their vasculature during the isolation process and have to rely on gradient-driven passive diffusion, which cannot provide adequate oxygen transport. Pancreatic islets (islets of Langerhans) are particularly susceptible due to their relatively large size, large metabolic demand, and increased sensitivity to hypoxia. Here, finite element method (FEM) based multiphysics models are explored to describe oxygen transport and cell viability in avascular islets both in static and in moving culture media.

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Section: Discussionsupporting

confidence: 82%

Section: Methodsmentioning

confidence: 96%

FEM-based oxygen consumption and cell viability models for avascular pancreatic islets

Buchwald

2009

Theor Biol Med Model

157

177

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“…Our results demonstrate that an implanted photosynthetic bioreactor can supply oxygen to transplanted islets and thus maintain islet viability/functionality. Supporting Information for this article is available online at http://www.thieme-connect.de/products Endocrine Care [8][9][10][11][12][13][14][15][16]. Moreover, cell necrosis resulting from hypoxia may increase the immune response to the graft [17].…”

Section: Introduction ▼mentioning

confidence: 99%

Oxygen Supply by Photosynthesis to an Implantable Islet Cell Device

et al. 2014

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Transplantation of islet cells is an effective treatment for type 1 diabetes with critically labile metabolic control. However, during islet isolation, blood supply is disrupted, and the transport of nutrients/metabolites to and from the islet cells occurs entirely by diffusion. Adequate oxygen supply is essential for function/survival of islet cells and is the limiting factor for graft integrity. Recently, we developed an immunoisolated chamber system for transplantation of human islets without immunosuppression. This system depended on daily oxygen supply. To provide independence from this external source, we incorporated a novel approach based on photosynthetically-generated oxygen. The chamber system was packed sandwich-like with a slab of immobilized photosynthetically active microorganisms (Synechococcus lividus) on top of a flat light source (LEDs, red light at 660 nm, intensity of 8 μE/m(2)/s). Islet cells immobilized in an alginate slab (500-1,000 islet equivalents/cm(2)) were mounted on the photosynthetic slab separated by a gas permeable silicone rubber-Teflon membrane, and the complete module was sealed with a microporous polytetrafluorethylene (Teflon) membrane (pore size: 0.4 μm) to protect the contents from the host immune cells. Upon illumination, oxygen produced by photosynthesis diffused via the silicone Teflon membrane into the islet compartment. Oxygen production from implanted encapsulated microorganisms was stable for 1 month. After implantation of the device into diabetic rats, normoglycemia was achieved for 1 week. Upon retrieval of the device, blood glucose levels returned to the diabetic state. Our results demonstrate that an implanted photosynthetic bioreactor can supply oxygen to transplanted islets and thus maintain islet viability/functionality.

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“…In these, a membrane was sometimes considered present, but its impact on the diffusion rate was not [8]. Complex modeling has been achieved by finite element methods [11,12,13,14,15,16,17] to allow the study of complex geometries, fluid dynamics, and the presence of anoxic cores and cell death within islets. These methods are powerful allowing even alternative geometries, such as hollow fibers [15,16,17], to be studied, but their development is costly, frequently requiring the use of multi-physics modeling software.…”

Section: Introductionmentioning

confidence: 99%

Modeling of reaction-diffusion transport into a core-shell geometry

King

Brown

Sargin

et al. 2019

Journal of Theoretical Biology

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Fickian diffusion into a core-shell geometry is modeled. The interior core mimics pancreatic Langerhan islets and the exterior shell acts as inert protection. The consumption of oxygen diffusing into the cells is approximated using Michaelis-Menten kinetics. The problem is transformed to dimensionless units and solved numerically. Two regimes are identified, one that is diffusion limited and the other consumption limited. A regression is fit that describes the concentration at the center of the cells as a function of the relevant physical parameters. It is determined that, in a cell culture environment, the cells will remain viable as long as the islet has a radius of around 142 µm or less and the encapsulating shell has a radius of less than approximately 283 µm. When the islet is on the order of 100 µm it is possible for the cells to remain viable in environments with as little as 4.6 × 10 −2 mol/m −3 O 2 . These results indicate such an encapsulation scheme may be used to prepare artificial pancreas to treat diabetes.

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Contributions of a Finite Element Model for the Geometric Optimization of an Implantable Bioartificial Pancreas

Cited by 16 publications

References 25 publications

FEM-based oxygen consumption and cell viability models for avascular pancreatic islets

FEM-based oxygen consumption and cell viability models for avascular pancreatic islets

Oxygen Supply by Photosynthesis to an Implantable Islet Cell Device

Modeling of reaction-diffusion transport into a core-shell geometry

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