Mathematical and Computational Modeling of Poroelastic Cell Scaffolds Used in the Design of an Implantable Bioartificial Pancreas
We present a multi-scale mathematical model and a novel numerical solver to study blood plasma flow and oxygen concentration in a prototype model of an implantable Bioartificial Pancreas (iBAP) that operates under arteriovenous pressure differential without the need for immunosuppressive therapy. Th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Fluids |
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| Online Access: | https://www.mdpi.com/2311-5521/7/7/222 |
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| author | Yifan Wang Sunčica Čanić Martina Bukač Charles Blaha Shuvo Roy |
| author_facet | Yifan Wang Sunčica Čanić Martina Bukač Charles Blaha Shuvo Roy |
| author_sort | Yifan Wang |
| collection | DOAJ |
| description | We present a multi-scale mathematical model and a novel numerical solver to study blood plasma flow and oxygen concentration in a prototype model of an implantable Bioartificial Pancreas (iBAP) that operates under arteriovenous pressure differential without the need for immunosuppressive therapy. The iBAP design consists of a poroelastic cell scaffold containing the healthy transplanted cells, encapsulated between two semi-permeable nano-pore size membranes to prevent the patient’s own immune cells from attacking the transplant. The device is connected to the patient’s vascular system via an anastomosis graft bringing oxygen and nutrients to the transplanted cells of which oxygen is the limiting factor for long-term viability. Mathematically, we propose a (nolinear) fluid–poroelastic structure interaction model to describe the flow of blood plasma through the scaffold containing the cells, and a set of (nonlinear) advection–reaction–diffusion equations defined on moving domains to study oxygen supply to the cells. These macro-scale models are solved using finite element method based solvers. One of the novelties of this work is the design of a novel second-order accurate fluid–poroelastic structure interaction solver, for which we prove that it is unconditionally stable. At the micro/nano-scale, Smoothed Particle Hydrodynamics (SPH) simulations are used to capture the micro/nano-structure (architecture) of cell scaffolds and obtain macro-scale parameters, such as hydraulic conductivity/permeability, from the micro-scale scaffold-specific architecture. To avoid expensive micro-scale simulations based on SPH simulations for every new scaffold architecture, we use Encoder–Decoder Convolution Neural Networks. Based on our numerical simulations, we propose improvements in the current prototype design. For example, we show that highly elastic scaffolds have a higher capacity for oxygen transfer, which is an important finding considering that scaffold elasticity can be controlled during their fabrication, and that elastic scaffolds improve cell viability. The mathematical and computational approaches developed in this work provide a benchmark tool for computational analysis of not only iBAP, but also, more generally, of cell encapsulation strategies used in the design of devices for cell therapy and bio-artificial organs. |
| first_indexed | 2024-03-09T03:26:58Z |
| format | Article |
| id | doaj.art-fa08cd95cecb4d85acd3a24463a1eddc |
| institution | Directory Open Access Journal |
| issn | 2311-5521 |
| language | English |
| last_indexed | 2024-03-09T03:26:58Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Fluids |
| spelling | doaj.art-fa08cd95cecb4d85acd3a24463a1eddc2023-12-03T15:02:06ZengMDPI AGFluids2311-55212022-07-017722210.3390/fluids7070222Mathematical and Computational Modeling of Poroelastic Cell Scaffolds Used in the Design of an Implantable Bioartificial PancreasYifan Wang0Sunčica Čanić1Martina Bukač2Charles Blaha3Shuvo Roy4Department of Mathematics, University of California, Irvine, CA 92697, USADepartment of Mathematics, University of California, Berkeley, CA 94720, USADepartment of Applied and Computational Mathematics and Statistics, University of Notre Dame, South Bend, IN 46556, USAMedical Center, University of California, San Francisco, CA 94143, USADepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94143, USAWe present a multi-scale mathematical model and a novel numerical solver to study blood plasma flow and oxygen concentration in a prototype model of an implantable Bioartificial Pancreas (iBAP) that operates under arteriovenous pressure differential without the need for immunosuppressive therapy. The iBAP design consists of a poroelastic cell scaffold containing the healthy transplanted cells, encapsulated between two semi-permeable nano-pore size membranes to prevent the patient’s own immune cells from attacking the transplant. The device is connected to the patient’s vascular system via an anastomosis graft bringing oxygen and nutrients to the transplanted cells of which oxygen is the limiting factor for long-term viability. Mathematically, we propose a (nolinear) fluid–poroelastic structure interaction model to describe the flow of blood plasma through the scaffold containing the cells, and a set of (nonlinear) advection–reaction–diffusion equations defined on moving domains to study oxygen supply to the cells. These macro-scale models are solved using finite element method based solvers. One of the novelties of this work is the design of a novel second-order accurate fluid–poroelastic structure interaction solver, for which we prove that it is unconditionally stable. At the micro/nano-scale, Smoothed Particle Hydrodynamics (SPH) simulations are used to capture the micro/nano-structure (architecture) of cell scaffolds and obtain macro-scale parameters, such as hydraulic conductivity/permeability, from the micro-scale scaffold-specific architecture. To avoid expensive micro-scale simulations based on SPH simulations for every new scaffold architecture, we use Encoder–Decoder Convolution Neural Networks. Based on our numerical simulations, we propose improvements in the current prototype design. For example, we show that highly elastic scaffolds have a higher capacity for oxygen transfer, which is an important finding considering that scaffold elasticity can be controlled during their fabrication, and that elastic scaffolds improve cell viability. The mathematical and computational approaches developed in this work provide a benchmark tool for computational analysis of not only iBAP, but also, more generally, of cell encapsulation strategies used in the design of devices for cell therapy and bio-artificial organs.https://www.mdpi.com/2311-5521/7/7/222bioartificial pancreasmathematical modelingfluid-poroelastic structure interaction |
| spellingShingle | Yifan Wang Sunčica Čanić Martina Bukač Charles Blaha Shuvo Roy Mathematical and Computational Modeling of Poroelastic Cell Scaffolds Used in the Design of an Implantable Bioartificial Pancreas Fluids bioartificial pancreas mathematical modeling fluid-poroelastic structure interaction |
| title | Mathematical and Computational Modeling of Poroelastic Cell Scaffolds Used in the Design of an Implantable Bioartificial Pancreas |
| title_full | Mathematical and Computational Modeling of Poroelastic Cell Scaffolds Used in the Design of an Implantable Bioartificial Pancreas |
| title_fullStr | Mathematical and Computational Modeling of Poroelastic Cell Scaffolds Used in the Design of an Implantable Bioartificial Pancreas |
| title_full_unstemmed | Mathematical and Computational Modeling of Poroelastic Cell Scaffolds Used in the Design of an Implantable Bioartificial Pancreas |
| title_short | Mathematical and Computational Modeling of Poroelastic Cell Scaffolds Used in the Design of an Implantable Bioartificial Pancreas |
| title_sort | mathematical and computational modeling of poroelastic cell scaffolds used in the design of an implantable bioartificial pancreas |
| topic | bioartificial pancreas mathematical modeling fluid-poroelastic structure interaction |
| url | https://www.mdpi.com/2311-5521/7/7/222 |
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