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

项目摘要 吸入颗粒和细菌的粘膜纤毛转运（MCT）对维持肺无菌性极其重要。在 在气管和支气管中，MCT是由粘膜下腺体产生的粘液链断裂驱动的 通过纤毛跳动。发现和发展更好的方法来研究颗粒MCT具有深远的意义 对肺系疾病发病机制的研究和新的治疗方法的探索产生了重要影响。由于其 重要的是，已经做出了巨大的努力来获得颗粒MCT，包括吸入放射性物质。 人/动物模型中的微圆盘，在气道上皮细胞培养物上应用颗粒，以及 气管组织然而，目前的方法在概括生物物理/生物化学气道方面存在不足。 环境，包括粘膜下腺体，并提供必要的解决方案，在研究MCT的自然 吸入的颗粒物为了解决未满足的需求，我们的总体目标是开发一种芯片上的气管， 研究精确控制的气道环境中微米/纳米级颗粒的MCT。我们的初步研究 展示了一种微流控装置的实现， 生理学和功能，命名为“气管芯片”。在拟议的研究中，我们的目标是评估颗粒MCT 在非浸没气道表面上使用气管芯片（目标1），并控制气道物理/化学 环境，以利用芯片上气管撞击颗粒MCT（目标2）。在拟议项目完成后， 我们期待三个结果。首先，我们将提供一种新型的气管芯片技术平台来研究气道 MCT粒子其次，我们将回答有关气道环境如何影响 MCT和气管芯片第三，本项目所获得的知识将广泛应用于其他肺 疾病，这将用于未来的R01应用。除了研究，拟议的项目将 进一步帮助候选人在工程前沿建立一个独特而充满活力的研究计划 和医药

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.