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

项目总结 吸入颗粒物和细菌的粘液纤毛运输(MCT)对维持肺部无菌非常重要。在……里面 气管和支气管，MCT是由粘膜下腺产生的粘液链断裂引起的 通过纤毛敲打。发现和发展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研究的影响和探索新的治疗方法。因为它的 重要的是，为获得微粒MCT，包括吸入放射性物质，已经做出了巨大努力 人/动物模型中的微盘，微粒在呼吸道上皮细胞培养上的应用 气管组织。然而，目前的方法不能概括生物物理/生化呼吸道。 环境，包括粘膜下腺，并为研究天然的MCT提供必要的解决方案 吸入的颗粒物。为了解决未得到满足的需求，我们的总体目标是开发一种单芯片气管，以 在精确控制的呼吸道环境中研究微/纳米颗粒的MCT。我们的初步研究 演示使用具有外延气管的微流控装置来维持呼吸道 生理和功能，命名为“芯片上的气管”。在拟议的研究中，我们的目标是评估粒子MCT 在非淹没的呼吸道表面使用单芯片气管(目标1)，并控制呼吸道物理/化学 使用芯片上气管影响颗粒MCT的环境(目标2)。在拟议的项目完成后， 我们预计会有三个结果。首先，我们将提供一个新型的单芯片气管技术平台来研究呼吸道 粒子MCT。第二，我们将回答有关呼吸道环境如何影响医疗效率的问题 单芯片气管插管的MCT。第三，在这个项目中获得的知识将广泛应用于其他肺 疾病，这将用于未来的R01应用程序。除了研究之外，拟议的项目还将 进一步帮助应聘者在工程前沿建立一个独特且充满活力的研究项目 还有医学。

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.