Collaborative Research: Mechanistic modeling of cell encapsulation
合作研究:细胞封装的机制建模
基本信息
- 批准号:2247000
- 负责人:
- 金额:$ 53.46万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-05-15 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Cell encapsulation is a biologically inspired technology that isolates live cells from the hostile environment. This is done by packaging the cells in a scaffold, which is encapsulated in a semi-permeable isolating membrane. The packaged cells are connected to the host’s vasculature via a tube (anastomosis graft) transporting oxygen and nutrients rich blood to the cells. The semi-permeable encapsulating membrane, located at the interface between the blood flow in the graft and the cell scaffold, is designed to block the host’s immune cells from attacking the transplanted cells, while allowing passage of oxygen and nutrients to the cells. A major challenge in cell encapsulation is sufficient oxygen and nutrients supply to maintain the long-term viability of cells. The main goal of this project is to develop a comprehensive multi-scale and multi-physics mathematical and computational framework modeling cell encapsulation. Using this framework, The PIs will address the long-term viability of encapsulated cells by (1) studying how hydrogel architecture and elasticity affect oxygen and nutrients supply to the cells, and by (2) exploring design of ultrafiltrate channels within the hydrogel to maximize oxygen and nutrients supply to the cells. The concept of cell encapsulation is highly relevant for bioartificial organs design and for controlled delivery of biological therapeutics. This interdisciplinary project will provide mentoring of undergraduate and graduate students at the interface between mathematics and biology. A new graduate course at Texas Tech will be introduced to train students in the state-or-the-art mathematical methods developed in this project. To promote participation of women in STEM, a series of Summer Workshops for High School girls will be organized at the UC Berkeley Mathematics Department with scientific visits to the UCSF Biodesign Laboratory. The goal of this project is to develop a comprehensive multi-scale, multi-physics mathematical and computational model of cell encapsulation for bioartificial organs design. At the macro-scale, two sets of time-dependent coupled models will be developed and analyzed: (1) a fluid-structure interaction (FSI) model between the Stokes/Navier-Stokes equations and the Biot membrane equations coupled to the nonlinear Biot poroelastic medium equations, and (2) a set of coupled nonlinear advection-reaction-diffusion equations defined on moving domains describing oxygen concentration in the encapsulated organ. Two partitioned schemes will be developed to solve the FSI problem and the coupled advection-reaction-diffusion problems. The numerical schemes will be designed to deal with the novel coupling conditions holding across a Biot poroelastic membrane interface, defined on a “mixed’’ 2D/3D domain. Stability analysis and convergence tests will be performed. To capture the impact of micro-scale hydrogel architecture on local hydraulic conductivity, Smoothed Particle Hydrodynamics (SPH) simulations will be used. The results of the SPH simulations will provide synthetic data for the Encoder-Decoder Convolution Neural Networks training (offline) to produce macro-scale parameters, such as the hydrogel permeability tensor, needed in macro-scale simulations. Validation and parameter estimation will be provided by the experiments at the UCSF Biodesign Laboratory. The results from this research will advance the knowledge in mathematical FSI involving poroelastic media and in coupled nonlinear advection-reaction-diffusion systems on moving domains. The outcomes of the findings will advance the knowledge in cell encapsulation for bioartificial organ design and in controlled delivery of biological therapeutics.This proposal is jointly funded by the Mathematical Biology Program of the Division of Mathematical Science (DMS), the Fluid Dynamics Program and the Engineering of Biomedical Systems (EBMS) Program, both in the Chemical, Bioengineering, Environmental, and Transport Systems (CBET) Division, Directorate for Engineering.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.
细胞封装是一种生物启发的技术,将活细胞从恶劣的环境中隔离出来。这是通过将细胞包装在支架中来完成的,支架被封装在半渗透隔离膜中。包装的细胞通过将富含氧气和营养物的血液输送到细胞的管(吻合移植物)连接到宿主的脉管系统。位于移植物中的血流和细胞支架之间的界面处的半渗透性封装膜被设计成阻止宿主的免疫细胞攻击移植的细胞,同时允许氧气和营养物质通过细胞。细胞包封的主要挑战是足够的氧气和营养物质供应,以维持细胞的长期活力。该项目的主要目标是开发一个全面的多尺度和多物理数学和计算框架来建模细胞封装。使用这个框架,PI将通过(1)研究水凝胶结构和弹性如何影响细胞的氧气和营养供应,以及(2)探索水凝胶内超滤液通道的设计,以最大限度地增加对细胞的氧气和营养供应,来解决封装细胞的长期生存能力。细胞包封的概念与生物人工器官设计和生物治疗剂的受控递送高度相关。这个跨学科的项目将提供指导的本科生和研究生之间的数学和生物学的接口。德克萨斯理工学院将推出一门新的研究生课程,以培养学生掌握本项目中开发的最先进的数学方法。为了促进妇女参与STEM,将在加州大学伯克利分校数学系组织一系列高中女生暑期讲习班,并对UCSF生物设计实验室进行科学访问。本研究的目标是建立一个多尺度、多物理场的细胞包封的数学和计算模型,用于生物人工器官的设计。在宏观尺度上,将开发和分析两组时间相关的耦合模型:(1)Stokes/Navier-Stokes方程和耦合到非线性毕奥多孔弹性介质方程的毕奥膜方程之间的流体-结构相互作用(FSI)模型,以及(2)一组耦合的非线性对流-反应-扩散方程,该方程定义在描述被包裹器官中的氧浓度的移动域上。两个分区格式将被开发来解决流固耦合问题和耦合对流-反应-扩散问题。数值方案将被设计为处理新的耦合条件,保持在一个毕奥多孔弹性膜界面,定义在一个“混合”的2D/3D域。将进行稳定性分析和收敛性测试。为了捕获微尺度水凝胶结构对局部水力传导性的影响,将使用平滑粒子流体动力学(SPH)模拟。SPH模拟的结果将为编码器-解码器卷积神经网络训练(离线)提供合成数据,以产生宏观尺度模拟所需的宏观尺度参数,例如水凝胶渗透性张量。验证和参数估计将由UCSF Biodesign实验室的实验提供。本研究的结果将促进多孔弹性介质中的数学流固耦合问题和运动域上的非线性对流-反应-扩散耦合问题的研究。这些发现的结果将推进生物人工器官设计的细胞包封和生物治疗剂的受控递送方面的知识。该提案由数学科学部(DMS)的数学生物学计划、流体动力学计划和生物医学系统工程(EBMS)计划共同资助,这两个计划都在化学、生物工程、环境和运输系统(CBET)部门,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。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Fluid-poroviscoelastic structure interaction problem with nonlinear coupling
非线性耦合的流体-多孔粘弹性结构相互作用问题
- DOI:
- 发表时间:2024
- 期刊:
- 影响因子:0
- 作者:Jeffrey Kuan, Suncica Canic
- 通讯作者:Jeffrey Kuan, Suncica Canic
Well-Posedness of Solutions to Stochastic Fluid–Structure Interaction
- DOI:10.1007/s00021-023-00839-y
- 发表时间:2022-03
- 期刊:
- 影响因子:1.3
- 作者:Jeffrey Kuan;S. Čanić
- 通讯作者:Jeffrey Kuan;S. Čanić
Existence of a weak solution to a regularized moving boundary fluid-structure interaction problem with poroelastic media
多孔弹性介质正则化移动边界流固耦合问题弱解的存在性
- DOI:10.5802/crmeca.190
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Kuan, Jeffrey;Čanić, Sunčica;Muha, Boris
- 通讯作者:Muha, Boris
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Suncica Canic其他文献
Suncica Canic的其他文献
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- 批准号:
2011319 - 财政年份:2020
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流弹性结构与纳维滑移边界条件的相互作用
- 批准号:
1613757 - 财政年份:2016
- 资助金额:
$ 53.46万 - 项目类别:
Standard Grant
Fluid-structure interaction with multi-layered structures: a new class of partitioned schemes
多层结构的流固耦合:一类新的分区方案
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1318763 - 财政年份:2013
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1263572 - 财政年份:2013
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流体-多层结构相互作用问题
- 批准号:
1311709 - 财政年份:2013
- 资助金额:
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1109189 - 财政年份:2011
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1015002 - 财政年份:2010
- 资助金额:
$ 53.46万 - 项目类别:
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血流的移动边界问题
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0806941 - 财政年份:2008
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$ 53.46万 - 项目类别:
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0443826 - 财政年份:2005
- 资助金额:
$ 53.46万 - 项目类别:
Continuing Grant
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