Organ on chip technology to evaluate engineered nanomaterial toxicity

评估工程纳米材料毒性的器官芯片技术

• 批准号: 9770858
• 负责人: KEVIN KIT PARKER
• 金额: $ 45.6万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9770858
• 关键词: Acute; Angiogenic Factor; Asthma; Behavior; Biological; Blood Vessels; Cardiac; Cell Survival; Cells; Chronic; Coupled; Dermal; Dermis; Development; Devices; Dimensions; Disease; Disease model; Dose; Drug Screening; Endothelial Cells; Endothelium; Engineering; Ensure; Epidermis; Evaluation; Exposure to; Extracellular Matrix; Fiber; Fibroblast Growth Factor; Fibroblasts; Film; Future; Histologic; Human; Human Engineering; Hydrogels; In Vitro; Individual; Infiltration; Interleukin-13; Intravenous; Laboratories; Measures; Metabolic; Modeling; Modernization; Molecular Weight; Muscle; Organ; Organ Model; Permeability; Pharmacology; Phenotype; Physiological; Population; Porosity; Property; Proteins; Resources; Route; Seeds; Skin; Skin Tissue; Standardization; Structure; Surface; System; Technology; Testing; Thick; Thinness; Tissue Engineering; Tissue Viability; Tissues; Topical application; Toxic effect; Toxicity Tests; Toxicology; Variant; Vascular Endothelial Cell; Vascular Endothelial Growth Factors; Vascular Endothelium; Vascular System; Venous; Work; asthmatic; base; body system; density; dermal exposure; experience; experimental study; exposed human population; exposure route; in vitro Model; keratinocyte; macrophage; mechanical properties; metabolic phenotype; nanofiber; nanomaterials; neovascularization; novel; organ on a chip; response; scaffold

PROJECT SUMMARY We propose to modernize in vitro toxicology testing to facilitate comprehensive evaluation of biological response profiles to engineered nanomaterials. To ensure that high-content evaluation of response profiles can be measured using human-relevant systems, our platform is based on organ-on-chip technologies presently used for pharmacology and in vitro disease models. We extend the capability of these systems by introducing novel exposure chips that recapitulate a variety of exposure routes and interface with existing organ chips. Nanomaterials administered through exposure chips to the underlying organs may elicit exposure route- dependent responses that we aim to quantify. Specific project aims include quantitative comparison of cardiac and airway tissue response profiles to engineered nanomaterials administered by direct exposure, through and endothelial barrier, through tissue engineered vasculature, or through a synthetic skin tissue. We focus on cardiac and airway organ models because they are established platforms that provide robust metrics of tissue viability, structure, and function, in response to pharmacological challenges. We extend the capabilities of these organ systems for nanomaterial toxicity testing with the addition of exposure chips. To model intravenous and topical delivery routes, successive variations of the exposure chips will recapitulate endothelial barrier properties and engineered dermal tissues with increasing fidelity. The proposed work builds on our laboratory’s expertise manufacturing and testing organ-on-chip in vitro toxicology platforms. Our team is a leader in this field, developing diverse organ models and exploring their interactions for drug screening and disease modeling applications. We have extensive experience fabricating modular organ chips and the proposed exposure chip will be broadly applicable to organ models beyond the original focus on cardiac and airway systems. Standardization of our organ chip manufacturing ensures that exposure chips can be interfaced with a broad and expanding arsenal or human organ models. Importantly, we expect this work will lead to future exposure chips encompassing an expanding number of delivery routes.

项目摘要 我们建议实现体外毒理学试验的现代化，以促进生物学的全面评价。 对工程纳米材料的反应概况。为了确保对响应配置文件的高内容评估能够 使用人类相关系统进行测量，我们的平台目前基于器官芯片技术 用于药理学和体外疾病模型。我们通过引入 新的曝光芯片，概括了各种曝光途径，并与现有的器官芯片接口。 通过暴露芯片向底层器官施用纳米材料可能会引发暴露途径- 我们要量化的依赖性反应。 具体的项目目标包括定量比较心脏和气道组织反应概况， 通过直接暴露、通过内皮屏障、通过组织给予工程纳米材料 工程化的脉管系统，或通过合成皮肤组织。我们专注于心脏和气道器官模型 因为它们是提供组织活力、结构和功能的稳健度量的已建立的平台， 对药理学挑战的反应。我们扩展了这些器官系统的能力， 毒性测试加上暴露芯片。为了模拟静脉内和局部给药途径， 暴露芯片的连续变化将概括内皮屏障特性 真皮组织的保真度越来越高。 拟议的工作建立在我们实验室的专业知识制造和测试器官芯片体外 毒理学平台我们的团队是这一领域的领导者，开发了各种器官模型，并探索其 药物筛选和疾病建模应用的相互作用。我们有丰富的经验， 模块化器官芯片和所提出的曝光芯片将广泛适用于器官模型， 最初专注于心脏和气道系统。我们的器官芯片制造标准化确保， 曝光芯片可以与广泛和不断扩展的武器库或人体器官模型接口。重要的是我们 预计这项工作将导致未来的曝光芯片涵盖越来越多的交付路线。