Hybrid Multiscale Methods with Applications in Biomaterials and Bioengineering

混合多尺度方法在生物材料和生物工程中的应用

• 批准号: 1913146
• 负责人: Yi Sun
• 金额: $ 17.91万
• 依托单位: University of South Carolina at Columbia
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1913146&HistoricalAwards=false
• 关键词: Hybrid; Multiscale; Methods; Applications; Biomaterials

On the research side, this project aims to develop experimentally guided, hybrid multiscale models and methods to study complex biological systems and problems arising in biomaterials and bioengineering (a) sprouting angiogenesis during vascularization; (b) bacterial swarming during biofilm formation. This research will have many benefits to multiscale problems and relevant applications in biomaterials, tissue regeneration and biomedical engineering, which include bioprinting technology for fabricating tissues and organs, study of cell motions, drug design and ultimately regenerative medicine. These methods can be used as hypothesis generating and testing tools for biologists and bioengineers. Through collaboration with experimentalists, the PI will develop a hybrid multiscale approach to better understand complex mechanisms in the vascularization and the biofilm growth. On the educational side, this project will not only provide multidisciplinary research training to graduate and undergraduate students, but also promote awareness and interest in computational mathematics and mathematical biology among underrepresented minority groups.For the thrust (a), motivated by new findings in sprouting angiogenesis in bioprinting technology, the PI will integrate models for angiogenic signaling pathways with that for the mechanical motion. In particular, we employ typically coarse-grained continuum models (reaction-diffusion (RD) systems) to describe the dynamics of vascular-endothelial-growth-factor (VEGF) and nutrients/oxygen, a mechanical model for the extra-cellular matrix (ECM) based on the finite element method (FEM), and couple a discrete multicellular lattice model based on the kinetic Monte Carlo (KMC) algorithm to describe the cellular dynamics. Communication between the microscale model and the continuum ones is carried out via a suite of multiscale protocols. For the thrust (b), the PI will study several mechanisms responsible for bacterial swarming during biofilm formation, such as bacterial chemotaxis, interaction between bacteria, bacterial shapes, etc. In the proposed hybrid agent-based model, bacteria are characterized by self-propelled particles (SPP) or self-propelled rods (SPR) and the dynamics of extracellular polymeric substances (EPS) in the environment is described by continuously changing fields. The multiscale model is described by a system of ordinary and partial differential equations. The research outcomes consist of a set of hybrid multiscale models, detailed implementation of the models, and accompanying in silico analysis tools for simulating tissue formation and ultimately 3D biofabrication involving angiogenesis and vascularization. The tools can provide efficient ways to systematically test the influence of individual cellular features under a spectrum of environmental conditions and to study the collective behavior of bacterial colonies.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.

在研究方面，该项目旨在开发实验指导的混合多尺度模型和方法，以研究在血管化期间生物材料和生物工程（a）发芽血管生成的复杂生物系统和问题； （b）生物膜形成过程中细菌蜂群。这项研究将在生物材料，组织再生和生物医学工程中的多尺度问题和相关应用中具有许多好处，其中包括用于制造组织和器官的生物打印技术，细胞运动的研究，药物设计以及最终再生医学。这些方法可以用作生物学家和生物工程师的假设生成和测试工具。通过与实验者的合作，PI将开发一种混合多尺度方法，以更好地了解血管化和生物膜生长中的复杂机制。 On the educational side, this project will not only provide multidisciplinary research training to graduate and undergraduate students, but also promote awareness and interest in computational mathematics and mathematical biology among underrepresented minority groups.For the thrust (a), motivated by new findings in sprouting angiogenesis in bioprinting technology, the PI will integrate models for angiogenic signaling pathways with that for the mechanical motion. In particular, we employ typically coarse-grained continuum models (reaction-diffusion (RD) systems) to describe the dynamics of vascular-endothelial-growth-factor (VEGF) and nutrients/oxygen, a mechanical model for the extra-cellular matrix (ECM) based on the finite element method (FEM), and couple a discrete multicellular lattice model based on the kinetic Monte Carlo (KMC)描述细胞动力学的算法。微观模型与连续模型之间的通信是通过一组多尺度协议进行的。对于推力（b），PI将研究几种在生物膜形成过程中细菌蜂拥而至的几种机制，例如细菌趋化性，细菌之间的相互作用，细菌，细菌形状等。在拟议的基于杂化剂的模型中，细菌在细菌中以自propelled颗粒（SPP）或自我保护（SPR）（SPR）（SPR）（SPR）（SPR）（SPR）（SPR）（SPR）（SPR）（SPR）（SPR）（SPRE）（SPR）（SPR）（SPR）（SPRE）（SPR）表征。环境通过不断变化的字段描述。多尺度模型由普通和部分微分方程的系统描述。该研究结果包括一组混合多尺度模型，模型的详细实现，并伴随着模拟组织形成的计算机分析工具，最终涉及血管生成和血管化的3D生物制作。这些工具可以提供有效的方法来系统地测试各种环境条件下单个细胞特征的影响，并研究细菌菌落的集体行为。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子优点和更广泛的影响审查标准来评估的值得通过评估的。

项目成果

Kinetic Monte Carlo simulations of bi-direction pedestrian flow with different walk speeds

不同步行速度双向行人流的动力学蒙特卡罗模拟

• DOI: 10.1016/j.physa.2020.124295
• 发表时间: 2020
• 期刊: Physica A: Statistical Mechanics and its Applications
• 作者: Sun, Yi

On a class of new nonlocal traffic flow models with look-ahead rules

一类新的具有前瞻规则的非局部交通流模型

• DOI: 10.1016/j.physd.2020.132663
• 发表时间: 2020
• 期刊: Physica D: Nonlinear Phenomena
• 作者: Sun, Yi;Tan, Changhui
• 通讯作者: Tan, Changhui

Accelerated kinetic Monte Carlo methods for general nonlocal traffic flow models

一般非局部交通流模型的加速动力学蒙特卡罗方法

• DOI: 10.1016/j.physd.2023.133657
• 发表时间: 2023
• 期刊: Physica D: Nonlinear Phenomena
• 作者: Sun, Yi;Tan, Changhui
• 通讯作者: Tan, Changhui

Application of the dynamic Monte Carlo method to pedestrian evacuation dynamics

• DOI: 10.1016/j.amc.2023.127876
• 发表时间: 2023-05
• 期刊: Appl. Math. Comput.
• 作者: Nutthavuth Tamang;Yi Sun