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

项目概要 吸入颗粒和细菌的粘膜纤毛转运（MCT）对于维持肺部无菌极为重要。在 气管和支气管，MCT 是由粘膜下腺产生的粘液丝断裂驱动的 通过纤毛跳动。发现和开发更好的方法来研究粒子 MCT 具有深远的意义 对肺部疾病发病机制的研究和新治疗方法的探索产生影响。由于其 重要性，已经付出了巨大的努力来获得粒子MCT，包括吸入放射性物质 人类/动物模型中的微盘，气道上皮细胞培养物上颗粒的应用，以及外植 气管组织。然而，当前的方法在概括生物物理/生化气道方面存在不足。 环境，包括粘膜下腺，并为研究自然的 MCT 提供必要的解决方案 吸入状颗粒。为了解决未满足的需求，我们的总体目标是开发一种气管芯片 研究精确控制气道环境中微米/纳米尺寸颗粒的 MCT。我们的初步研究 演示如何使用带有外植气管的微流体装置来维持气道 生理学和功能，命名为“气管芯片”。在拟议的研究中，我们的目标是评估粒子 MCT 在带有气管芯片的非浸没气道表面上（目标 1），并控制气道物理/化学 影响颗粒 MCT 的气管芯片（目标 2）。拟议项目完成后， 我们预计会出现三种结果。首先，我们将提供一种新颖的气管芯片技术平台来研究气道 颗粒MCT。其次，我们将回答有关气道环境如何影响效率的问题。 带气管芯片的 MCT。第三，该项目获得的知识将广泛应用于其他肺部 疾病，这将用于未来的 R01 应用。除了研究之外，拟议的项目还将 进一步帮助候选人在工程前沿建立独特且充满活力的研究计划 和医学。

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.