Developing Trachea-on-a-chip to Study Particle Mucociliary Transport in Airways

开发气管芯片来研究气道中的颗粒粘液纤毛运输

• 批准号: 10671564
• 负责人: Yuliang Xie
• 金额: $ 18.65万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10671564
• 关键词: 3D Print; Address; Affect; Air; Airway Disease; Algorithms; Alveolus; Animal Model; Apical; Asthma; Bacteria; Bicarbonates; Biochemical; Biomedical Engineering; Biophysics; Bronchi; Cartilage; Cell Culture Techniques; Chemicals; Chronic Obstructive Pulmonary Disease; Cilia; Cystic Fibrosis; Development; Devices; Disease; Engineering; Environment; Family suidae; Fluorescence; Future; Gland; Goals; Host Defense; Human; Humidity; Impairment; Individual; Inhalation; Intake; Investigation; Ion Channel; Knowledge; Lab On A Chip; Lung; Lung diseases; Medicine; Methods; Microfluidic Microchips; Mucociliary Clearance; Mucous body substance; Names; Outcome; Particulate; Pathogenesis; Performance; Perfusion; Periodicals; Physical environment; Physiology; Primary Ciliary Dyskinesias; Process; Pulmonary Cystic Fibrosis; Radioactive; Relaxation; Research; Resolution; Science; Speed; Sterility; Stretching; Structure; Submucosa; Surface; System; Techniques; Tissue Viability; Tissues; Trachea; Visualization; aerosolized; airway epithelium; biophysical properties; cartilaginous; engineering design; experience; falls; in vivo; nanoparticle; novel; novel therapeutics; nutrition; particle; pathogen; programs; viscoelasticity

PROJECT SUMMARY Mucociliary transport (MCT) of inhaled particles and bacteria is extremely important to maintain lung sterility. In trachea and bronchi, MCT is driven by breakage of mucus strands that emerge from submucosal glands through cilia beating. Discovery and development of better methods to investigate particle MCT has profound impacts on the study of lung disease pathogenesis and exploration of new therapeutic methods. Because of its importance, tremendous efforts have been made to access particle MCT, including inhalation of radioactive micro-disks in human/animal models, application of particles on airway epithelial cell cultures, and explanted trachea tissues. However, current methods fall short in recapitulating the biophysical/biochemical airway environment, including submucosal glands, and providing necessary resolution in studying MCT of natural inhaled-like particles. To address the unmet need, our overall objective is to develop a trachea-on-a-chip to study MCT of micro/nano-sized particles in precisely controlled airway environments. Our preliminary studies demonstrate the implementation of a microfluidic device with an explanted trachea to maintain airway physiology and function, named “trachea-on-a-chip”. In the proposed research, we aim to assess particle MCT on a non-submerged airway surface with trachea-on-a-chip (Aim 1), and control airway physical/chemical environment to impact particle MCT with trachea-on-a-chip (Aim 2). Upon completion of the proposed project, we expect three outcomes. First, we will deliver a novel trachea-on-a-chip technical platform to study airway particle MCT. Second, we will answer questions as to how the airway environment impacts the efficiency of MCT with trachea-on-a-chip. Third, the knowledge obtained in this project will be broadly applied to other lung diseases, which will be used for future R01 applications. In addition to research, the proposed project will further help the candidate to build a unique and vibrant research program on the cutting edge of engineering and medicine.

项目摘要 遗传颗粒和细菌的粘膜纤毛转运（MCT）对于维持肺无菌性非常重要。 气管和支气管，MCT是由从粘膜粘膜中脱落的粘液链断裂驱动的 通过纤毛跳动。发现和开发更好的方法来研究粒子MCT具有深刻的 对肺部疾病发病机理的研究和新治疗方法的探索的影响。因为它 重要的是，已经为进入粒子MCT做出了巨大的努力，包括吸入放射性 人/动物模型中的微盘，颗粒在气道上皮细胞培养物上的应用并植入了 气管组织。但是，当前方法在概括生物物理/生化气道方面缺乏 环境，包括粘膜烤架，并在研究自然的MCT方面提供必要的解决方案 吸入样颗粒。为了满足未满足的需求，我们的总体目标是开发芯片的气管 在精确控制的气道环境中的微/纳米大小颗粒的研究MCT。我们的初步研究 演示具有露天气管的微流体设备的实施以维护气道 生理学和功能，称为“芯片气管”。在拟议的研究中，我们旨在评估粒子MCT 在带有气管片的非吸气气道表面上（AIM 1），并控制气道物理/化学 用气管芯片撞击颗粒MCT的环境（AIM 2）。拟议项目完成后， 我们期望三个结果。首先，我们将提供一个新颖的气管芯片技术平台来研究气道 粒子MCT。其次，我们将回答有关气道环境如何影响效率的问题 MCT带气管片。第三，该项目获得的知识将广泛应用于其他肺部 疾病，将用于将来的R01应用程序。除研究外，拟议的项目还将 进一步帮助候选人在工程的最前沿建立独特而充满活力的研究计划 和医学。