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).

慢性呼吸道抑制作用，例如哮喘或慢性阻塞性肺部疾病是近10亿人的主要人物，继续使用tarban社会。 ”（MCC）微观柔性纤毛嵌入在两个流体环境中的纤毛和可变形导管中的时间剥夺呼吸空气流动。这是开发出能够研究人类肺部流动动力学的新数值工具的长期目标。已经开发了基于双方的晶格玻尔兹 /浸入边界方法的求解器。简单的流体动力，在上皮表面上具有更少的能量消耗的支气管。微观量表将开发一个宏观的模型，能够模拟支气管上部的严重性变化，这些微观和宏观模型将与实验数据进行比较环境与加拿大的工程师，生物学家和临床医生相互作用。纤毛或鞭毛的运动涉及：f海洋动物，微流体装置中的泵送和混合以及其他人体器官（法拉皮式）管中的流体转运，眼睛）。