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用于治疗1型糖尿病的可植入的生物人工胰腺的最佳设计。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，并将含两个纳米孔的半渗透膜之间的含细胞的培养基封装，以阻止患者的免疫电池攻击移植。封装的组织移植是消除长期使用免疫抑制剂的一种新型方法，这是移植疗法的主要挑战之一。纳米孔膜的设计旨在阻断免疫细胞，同时使营养物质通过尽可能长。 UCSF生物设计实验室主任S. Roy博士周围的团队正在探索一种可植入的生物人工胰腺的设计，该胰腺胰腺将植入患者的手臂，并与动脉和静脉相连，类似于动脉植物的嫁接。生物人工胰腺发展的主要挑战是通过提供足够的营养物质来维持长时间的移植细胞存活，其中氧气是限制因素。计划在这项研究的几个方面参与研究生和本科生以及高中生（尤其是女孩）。拟议项目的协同方法将提供第一，长期可行的生物人工胰腺，而无需进行免疫抑制治疗。该项目介绍了多物理，多规模数学和计算模型的开发，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。可植入的生物人工胰腺将由一个包裹的腔室组成，其中包含称为胰岛的移植胰腺细胞，以及将腔室连接到患者心血管系统的移植物。封装室被建模为一种多层的毛弹性培养基，该培养基由两个半渗透膜组成，这些膜封装了固定细胞的孔弹性凝胶。封装策略可防止宿主的免疫细胞攻击移植。提出的数学宏尺度模型捕获了包裹的多层毛弹性胰岛室内的血清过滤，以及血流与动脉植物的血液之间的流体结构相互作用，将血液带到胰岛腔中。为了研究对移植细胞的氧气供应，流体结构相互作用模型与三个非线性对流反应扩散模型耦合，描述了管状移植物中的氧浓度，毛弹性膜和胰岛腔室。提出了一个新的分区，松散的耦合方案，用于该问题的数值解。在微尺度上，将使用平滑的颗粒流体动力求解器来研究细毛弹性培养基结构对氧气供应对移植细胞的影响。深度神经网络将用于研究参数估计。该奖项反映了NSF的法定任务，并通过使用基金会的知识分子优点和更广泛的影响评估标准来评估，被认为是宝贵的支持。