Lung-on-a-chip enables dynamic imaging of pulmonary lung tissue in response to aerosolized nanoparticles

芯片肺能够响应雾化纳米粒子对肺组织进行动态成像

基本信息

批准号：
9759650
负责人：
Whitney Sinclair
金额：
$ 4.55万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-01 至 2022-04-19
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9759650
关键词：
Acute Adhesions Adverse effects Alveolar Animal Model Artificial nanoparticles Biochemical Biological Blood Vessels Blood capillaries Blood flow Body Regions Breathing Cell Culture Techniques Cell Death Cells Chemistry Chronic Coculture Techniques Complex Disease Drug Delivery Systems Endothelial Cells Endothelium Environment Epithelial Epithelial Cells Epithelium Ethics Exposure to Extravasation Goals Health Hour Human Human body Image Imaging Techniques Inflammation Inflammation Mediators Inflammatory Response Intercellular Fluid Intercellular Junctions Liquid substance Lung Lung Inflammation Measurement Mechanics Methods Microfluidic Microchips Microfluidics Modeling Monitor Pharmaceutical Preparations Physiological Physiology Preclinical Testing Prevalence Procedures Production Resolution Shapes Signal Transduction Stimulus Stretching Structure of parenchyma of lung Surface Suspensions Technology Therapeutic Agents Thrombin Time Tissue Harvesting Tissues Toxic Environmental Substances Toxic effect Vascular Endothelium aerosolized consumer product cytokine design environmental particulate experimental study fluid flow hydrodynamic flow in vivo insight live cell imaging lung imaging mechanical force migration nanoparticle nanoparticle exposure organ on a chip physiologic model response tissue culture tool two-dimensional uptake

项目摘要

Project Summary Nanoparticles are moving towards use as consumer products and therapeutic agents, and are gaining prevalence as environmental toxins. There is increasing concern on the impact that nanoparticles have on human health, specifically the lung. The lung is the most susceptible region of the body to interact with environmental particulates. Current studies of nanoparticle interaction with cells lacks insight on the mechanisms that results in inflammation and cell death. Nanoparticle exposure in static monocultures may not predict the complex biochemical responses triggered in the human lung. Expensive, ethically challenged animal models, lack the capability for mechanistic studies. Whereas, lung-on-a-chip microfluidic platforms offer increasingly sophisticated methods to study the in vivo lung response. These platforms do so by applying hydrodynamic and mechanical forces to cocultures of endothelial and differentiated epithelial cells to mimic the physiological environment within the alveolar-capillary interface. There is an increasing need to use these dynamic platforms to study the interaction of nanoparticles on lung tissue. To this end, my fabricated lung-on-a-chip platform enables monitoring intercellular fluid leakage and live cell imaging in response to induced inflammation. With these tools, the project seeks to use dynamic imaging to study the impact of aerosolized nanoparticles on lung tissue. The tissue will be monitored for the progression of inflammation and nanoparticle migration.

项目概要纳米颗粒正逐渐用作消费品和治疗剂，并且作为环境毒素正在日益流行。人们越来越担心其影响纳米粒子对人类健康，特别是肺部有影响。肺部是最容易受影响的部位身体与环境颗粒物相互作用。纳米粒子相互作用的最新研究细胞缺乏对导致炎症和细胞死亡的机制的了解。静态单一培养中的纳米颗粒暴露可能无法预测复杂的生化反应在人的肺部触发。昂贵的、道德上受到挑战的动物模型，缺乏能力用于机理研究。然而，片上肺微流体平台提供了越来越多的研究体内肺部反应的复杂方法。这些平台通过申请来做到这一点内皮细胞和分化上皮细胞共培养的水动力和机械力模拟肺泡毛细血管界面内的生理环境。有一个越来越需要使用这些动态平台来研究纳米粒子对肺部的相互作用组织。为此，我制作的片上肺平台能够监测细胞间液响应诱导炎症的渗漏和活细胞成像。有了这些工具，项目试图利用动态成像来研究雾化纳米颗粒对肺组织的影响。将监测组织的炎症进展和纳米颗粒迁移。