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CRII: OAC: A Hybrid Finite Element and Molecular Dynamics Simulation Approach for Modeling Nanoparticle Transport in Human Vasculature

CRII：OAC：一种混合有限元和分子动力学模拟方法，用于模拟人体脉管系统中纳米颗粒的传输

基本信息

批准号：
1755779
负责人：
Ying Li
金额：
$ 17.5万
依托单位：
University of Connecticut
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-03-01 至 2023-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1755779&HistoricalAwards=false
关键词：
CRII OAC Hybrid Finite Element

项目摘要

Through nanomedicine significant methods are emerging to deliver drug molecules directly to diseased areas for cancer treatment. Targeted drug delivery is one of the most promising approaches which relies on nanoparticles (NPs) that carry and release drugs. The therapeutic efficacy of NP-based drug carriers is determined by the proper concentration of drug molecules at the lesion site. NPs need to be delivered directly to the diseased tissues while minimizing their uptake by other tissues, thereby reducing the potential harm to healthy tissue. Therefore, the design of these NPs and hence the efficacy of the targeted drug delivery could be significantly improved by understanding how the drugs carried by NPs are transported and dispersed in human body. This project proposes a set of computational tools to model and investigate the transport and dispersion of NPs in human vasculature. This, in turn, can provide better imaging sensitivity, therapeutic efficacy and lower toxicity of NP-based drug carriers. The multidisciplinary nature of the project also brings together concepts from biology, engineering and computer science to educate the next generation of computational biologists, scientists and engineers. This research, thus, aligns with the NSF mission to promote the progress of science and to advance the national health, prosperity and welfare. The technical objective of this project is to create a hybrid finite element and molecular dynamics computational approach for modeling NP transport and adhesion in human vasculature. The realistic geometry of vascular network and fluid dynamics of blood flow are accurately captured through the finite element model. The microscopic interactions between NPs and red blood cells within blood flow and adhesion of NPs to vessel wall are resolved through the molecular dynamics simulation. A robust and efficient coupling interface is built to couple the finite element and molecular dynamics solvers. Specifically, this project aims to 1) create a multiscale and multiphysics computational model for predicting the vascular dynamics of NPs under the influence of realistic geometrical and physiochemical features of human vasculature; 2) craft an interface coupling technique that enhances computational accuracy and predictability by coupling the finite element and molecular dynamics solvers; 3) build testsuits for multiscale and multiphysics simulations for coupled solution error and convergence analysis; and 4) advance the current cyberinfrastructure to accelerate the material design process and enrich the cyber-enabled materials design community. Such a computational method can be used to explore how the vascular dynamics of NPs will be affected by their size, shape, surface and stiffness properties, as well as complex geometry of human vasculature. The simulation results can further guide experimentalists to design NP-mediated drug delivery platforms that optimally accumulate within diseased tissue to provide better imaging sensitivity, therapeutic efficacy and lower toxicity.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.

通过纳米医学，将药物分子直接输送到患病区域进行癌症治疗的重要方法正在出现。靶向给药是最有前途的方法之一，它依赖于携带和释放药物的纳米颗粒。np基药物载体的治疗效果取决于病灶部位药物分子的适当浓度。NPs需要直接递送到病变组织，同时尽量减少其他组织对其的吸收，从而减少对健康组织的潜在危害。因此，通过了解NPs所携带的药物如何在人体内运输和分散，可以大大提高这些NPs的设计，从而提高靶向给药的效果。本项目提出了一套计算工具来模拟和研究NPs在人体脉管系统中的运输和分散。这反过来又可以为np基药物载体提供更好的成像灵敏度、治疗效果和更低的毒性。该项目的多学科性质也汇集了生物学、工程学和计算机科学的概念，以教育下一代计算生物学家、科学家和工程师。因此，这项研究符合美国国家科学基金会促进科学进步和促进国家健康、繁荣和福利的使命。该项目的技术目标是创建一种混合有限元和分子动力学计算方法，用于模拟人体脉管系统中的NP运输和粘附。通过有限元模型准确地捕捉了血管网络的真实几何形状和血流的流体动力学。通过分子动力学模拟，解析了血流中NPs与红细胞的微观相互作用以及NPs与血管壁的粘附。建立了一个鲁棒、高效的耦合界面，实现了有限元和分子动力学求解器的耦合。具体而言，本项目旨在1)建立一个多尺度和多物理场的计算模型，用于预测NPs在人体血管的真实几何和物理化学特征影响下的血管动力学；2)设计界面耦合技术，通过将有限元和分子动力学求解器耦合来提高计算精度和可预测性；3)构建多尺度和多物理场模拟测试套件，用于耦合解误差和收敛分析；4)推进当前的网络基础设施，加快材料设计过程，丰富网络材料设计社区。这种计算方法可以用来探索NPs的血管动力学如何受到其大小、形状、表面和刚度特性以及人体血管系统的复杂几何形状的影响。模拟结果可以进一步指导实验人员设计np介导的药物传递平台，使其在病变组织内最佳积累，从而提供更好的成像灵敏度、治疗效果和更低的毒性。该奖项反映了美国国家科学基金会的法定使命，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（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mechanical Resilience of Biofilms toward Environmental Perturbations Mediated by Extracellular Matrix

DOI：
10.1002/adfm.202110699
发表时间：
2022-03
期刊：
Advanced Functional Materials
影响因子：
19
作者：
Qiuting Zhang;Danh-Truong Nguyen;Jung-Shen B. Tai;XJ Xu;Japinder S. Nijjer;Xin Huang;Y. Li;Jing Yan
通讯作者：
Qiuting Zhang;Danh-Truong Nguyen;Jung-Shen B. Tai;XJ Xu;Japinder S. Nijjer;Xin Huang;Y. Li;Jing Yan

Shape-Dependent Transport of Microparticles in Blood Flow: From Margination to Adhesion