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A Computational Approach to the Design of a Bioartificial Pancreas

生物人工胰腺设计的计算方法

基本信息

批准号：
2011319
负责人：
Suncica Canic
金额：
$ 30万
依托单位：
University of California-Berkeley
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2011319&HistoricalAwards=false
关键词：
Computational Approach Design Bioartificial Pancreas

项目摘要

The main goal of this project is optimal design of an implantable, bioartificial pancreas for the treatment of Type 1 diabetes. The design is based on transplanting the healthy pancreatic cells into a gel medium (agarose gel), and encapsulating the cell-containing medium between two nanopore semi-permeable membranes to block the patient's immune cells from attacking the transplant. Encapsulated tissue transplantation is a novel approach to eliminating long-term use of immunosuppressants, which is one of the major challenges in transplantation therapy. The nanopore membranes are designed to block the immune cells while allowing passage of nutrients to keep the transplant viable as long as possible. The team around the collaborator Dr. S. Roy, Director of the Biodesign Laboratory at UCSF, is exploring a design of an implantable bioartificial pancreas, which will be implanted in the patient's arm, and connected to an artery and a vein similar to an arterio-venous graft. The key challenge in the development of the bioartificial pancreas is maintaining the survival of transplanted cells for an extended period of time, by providing sufficient access to nutrients, of which oxygen is the limiting factor. Involvement of graduate and undergraduate students, as well as high school students (particularly girls), in several aspects of this research is planned. The synergistic approach to the proposed project will provide a first, long-term viable implantable bioartificial pancreas without the need for immunosuppressive therapy. This project addresses the development of a multi-physics, multi-scale mathematical and computational model to study the design of an implantable, bioartificial pancreas for the treatment of Type 1 diabetes. The implantable, bioartificial pancreas will consist of an encapsulated chamber containing the transplanted pancreatic cells called islets, and a graft connecting the chamber to the patient’s cardiovascular system. The encapsulation chamber is modeled as a multi-layered poroelastic medium consisting of two semi-permeable membranes encapsulating a poroelastic gel holding the cells. The encapsulation strategy prevents the host’s immune cells from attacking the transplant. The proposed mathematical macro-scale model captures filtration of blood serum within the encapsulated multi-layered poroelastic islet chamber, and the fluid-structure interaction between the blood flow and the arterio-venous graft carrying blood to the islet chamber. To study oxygen supply to the transplanted cells, the fluid-structure interaction model is coupled to three nonlinear advection-reaction-diffusion models describing oxygen concentration in the tubular graft, in the poroelastic membrane, and in the islet chamber. A novel partitioned, loosely coupled scheme for the numerical solution of this problem is proposed. At the micro-scale, a Smoothed Particle Hydrodynamics solver will be used to study the influence of the fine poroelastic medium structure on oxygen supply to the transplanted cells. Deep Neural Networks will be used to study parameter estimation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该项目的主要目标是优化设计用于治疗1型糖尿病的可植入生物人工胰腺。该设计基于将健康的胰腺细胞移植到凝胶培养基（琼脂糖凝胶）中，并将含有细胞的培养基封装在两个纳米孔半透膜之间，以阻止患者的免疫细胞攻击移植物。包埋组织移植是一种消除长期使用免疫抑制剂的新方法，这是移植治疗的主要挑战之一。纳米孔膜被设计成阻止免疫细胞，同时允许营养物质通过，以保持移植物尽可能长时间地存活。团队围绕合作者S.加州大学旧金山分校生物设计实验室主任罗伊正在探索一种可植入的生物人工胰腺的设计，这种胰腺将被植入患者的手臂，并连接到类似于动静脉移植物的动脉和静脉。开发生物人工胰腺的关键挑战是通过提供足够的营养物质来维持移植细胞的存活时间延长，其中氧气是限制因素。计划让研究生和本科生以及高中生（特别是女生）参与这项研究的几个方面。该项目的协同方法将提供第一个长期可行的可植入生物人工胰腺，而无需免疫抑制治疗。该项目致力于开发多物理，多尺度数学和计算模型，以研究用于治疗1型糖尿病的可植入生物人工胰腺的设计。这种可植入的生物人工胰腺将由一个包含移植胰腺细胞（称为胰岛）的密封腔室和一个连接该腔室与患者心血管系统的移植物组成。包封室被建模为多层多孔弹性介质，其由两个半渗透膜组成，所述半渗透膜包封保持细胞的多孔弹性凝胶。包封策略防止宿主的免疫细胞攻击移植物。所提出的数学宏观尺度模型捕获封装的多层多孔弹性胰岛腔室内的血清的过滤，以及血流与将血液运送到胰岛腔室的动静脉移植物之间的流体-结构相互作用。为了研究向移植细胞的供氧，将流体-结构相互作用模型耦合到三个非线性对流-反应-扩散模型，其描述了管状移植物中、多孔弹性膜中和胰岛室中的氧浓度。提出了一种新的分区的，松耦合的数值求解方案，该问题。在微观尺度上，将使用光滑粒子流体动力学求解器来研究细多孔弹性介质结构对向移植细胞供氧的影响。深度神经网络将用于研究参数估计。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。