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

• 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
• 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

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.

项目摘要 纳米颗粒正在被用作消费品和治疗剂，以及 以环境毒素的形式流行起来。人们越来越担心这样做的影响 纳米颗粒对人类健康有影响，特别是对肺部。肺是最易受影响的部位。 与环境中的颗粒物相互作用。纳米粒子相互作用的研究现状 对导致炎症和细胞死亡的机制缺乏洞察力。 纳米颗粒在静态单一培养中的暴露可能不能预测复杂的生化反应 在人的肺里触发。昂贵的，有道德挑战的动物模型，缺乏能力 用于机械学研究。然而，单芯片肺微流控平台提供了越来越多的 研究活体肺反应的复杂方法。这些平台通过应用 内皮细胞与分化上皮细胞共培养的水动力和机械力 以模拟肺泡-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颗粒与肺部的相互作用 组织。为此，我制造的单芯片肺平台能够监测细胞间液体 对诱导的炎症作出反应的渗漏和活细胞成像。有了这些工具，项目 寻求使用动态成像来研究雾化纳米颗粒对肺组织的影响。 组织将被监测炎症和纳米颗粒迁移的进展。