Multiscale simulation of the respiratory epithelium: towards the development of a numerical tool to model human lungs

呼吸道上皮的多尺度模拟：开发模拟人类肺部的数值工具

• 批准号: RGPIN-2020-05058
• 负责人: Poncet, Sébastien
• 金额: $ 4.01万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=739860
• 关键词: Multiscale; simulation; respiratory; epithelium; towards

Chronic respiratory diseases such as asthma or chronic obstructive pulmonary disease are a major health problem affecting almost 1 billion people, a number that continues to grow due to the increased pollution in urban societies. At the root of these respiratory problems is a transport phenomenon that takes place in the lungs, named the "mucociliary clearance" (MCC), with a fascinating physics involving mass exchanges through the epithelium, the coordinated beating of microscopic flexible cilia embedded in a two-fluid environment and the time-dependent respiratory air flow in deformable conduits. The long-term objective of this present program is to develop new numerical tools able to investigate the flow dynamics in human lungs. Compared to heart, these are an even more challenging organ for numerical methods mainly because of their multiscale nature (from few microns for the cilia length to centimeters for the trachea's diameter) and complex geometry (23 generations of dichotomous branching). Through my former Discovery grant, a first solver based on the coupled lattice Boltzmann / immersed boundary method has been developed. The beating of cilia carpets has been simulated in a two-phase fluid medium with different properties. The results showed that a coordinated motion of cilia (metachrony) may emerge due to a simple hydrodynamic retroaction. Metachronal waves moving in the opposite direction compared to the main flow were found to better transport bronchial mucus with less energy consumption. Numerical developments are however still required to simulate more representative conditions at the epithelium surface then for the whole respiratory tract. It includes the modelling of the non-Newtonian behavior of bronchial mucus, the mass exchanges at the epithelium surface (porous medium), the three-dimensional cilia beating pattern, the elastic nature of the bronchial tree during breathing and the superimposed air flow. The new insights gained at the microscopic scale will serve to develop a macroscale model able to simulate several generations in the upper part of the bronchial tree. These micro- and macroscale models will be systematically compared to experimental data from new experimental facilities developed at Université de Sherbrooke. Eight highly qualified personnel will be trained during this program and evolved in a very stimulating environment, interacting with engineers, biologists and clinicians. In Canada, asthma is the third most common chronical disease with 3 millions of patients, inducing around $1.6 billion costs to the country. A better understanding of MCC from a mechanical point of view may serve to better manage such diseases. It will also pave the road to other applications where the coordinated motion of cilia or flagella is involved: the fluid propulsion of marine animals, the pumping and mixing in microfluidic devices and the fluid transport in other human organs (brain, Fallopian tubes, eyes).

诸如哮喘或慢性阻塞性肺部疾病之类的慢性呼吸道疾病是影响近10亿人的主要健康问题，由于城市社会污染的增加，这一数字不断增长。 At the root of these respiratory problems is a transport phenomenon that takes place in the lungs, named the "mucociliary clearance" (MCC), with a fascinating physics involving mass exchanges through the epithelium, the coordinated beating of Microscopic flexible cilia embedded in a two-fluid environment and the time-dependent respiratory air flow in deformable conduits.本计划的长期目标是开发能够研究人肺流动动态的新数值工具。与心脏相比，这些是数值方法的挑战器官，主要是因为它们具有多尺度性质（从纤毛长度的几微米到气管直径的厘米）和复杂的几何形状（23代二分分支）。通过我以前的Discovery Grant，已经开发了基于耦合晶格Boltzmann /沉浸边界方法的第一个求解器。在具有不同特性的两相流体培养基中模拟了纤毛地毯的打击。结果表明，由于简单的水动力追溯，纤毛（Metachrony）的协调运动可能会出现。与主流相比，与主流动相比，在相反的方向上移动的基质波可以更好地运输支气管粘液，而能量消耗较少。但是，对于整个呼吸道，仍需要数值发展来模拟上皮表面的更具代表性的条件。它包括对支气管粘液的非牛顿行为的建模，上皮表面（多孔培养基）的质量交换，三维的纤毛跳动模式，呼吸过程中支气管树的弹性性质和叠加的空气流动。在微观量表上获得的新见解将有助于开发一个能够模拟支气管树上部几代人的宏观模型。这些微观和宏观模型将与来自Sherbrooke大学开发的新实验设施的实验数据进行系统的比较。在该计划中将对八名高素质的人员进行培训，并在非常刺激的环境中发展，并与工程师，生物学家和临床医生互动。在加拿大，哮喘是第三大常见的慢性病，​​有300万名患者，该国诱发了约16亿美元的费用。从机械的角度，更好地了解MCC可以更好地治疗此类疾病。它还将在涉及纤毛或鞭毛的协调运动的其他应用中铺平道路：海洋动物的液体推进，微流体设备中的泵送和混合以及其他人体器官（大脑，输卵管，眼睛）中的流体运输。