Disc-on-a-chip: microfluidic nutrition and biomechanical loading integrated mouse disc culture system

Disc-on-a-chip：微流控营养和生物力学加载集成小鼠椎间盘培养系统

• 批准号: 9750632
• 负责人: XUDONG J. LI
• 金额: $ 21.32万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9750632
• 关键词: 3-Dimensional; Address; Adopted; Age; Area; Automation; Back Pain; Biochemical; Biological Assay; Biological Process; Biology; Biomechanics; Biomimetics; Bioreactors; Blood Circulation; Cells; Clinical Research; Consumption; Cues; Culture Media; Custom; Data; Development; Device Designs; Devices; Disease; Disease model; Drug Evaluation; Drug Screening; Ensure; Environment; Etiology; Functional disorder; Future; Genes; Genetic; Genetic study; Goals; Growth Factor; Health; Hydrostatic Pressure; In Vitro; Individual; Inflammatory; Intervertebral disc structure; Investigation; Laboratory Research; Liquid substance; Longevity; Low Back Pain; Mechanical Stress; Mechanics; Metabolism; Methodology; Microfabrication; Microfluidic Microchips; Microfluidics; Miniaturization; Modeling; Mus; Nutrient; Nutritional; Organ Culture Techniques; Outcome; Oxygen; Pathology; Pharmaceutical Preparations; Phenotype; Physiological; Prevalence; Printing; Process; Production; Protocols documentation; Reagent; Research; Research Personnel; Running; Sampling; Solid; System; Technology; Therapeutic; Time; Toxicology; Vertebral column; Virulence Factors; clinically relevant; cost; cytokine; design; disability; drug development; drug discovery; growth differentiation factor 5; in vivo; interest; intervertebral disk degeneration; mechanical load; monolayer; multidisciplinary; novel; novel therapeutics; nutrition; organ on a chip; precision medicine; prototype; rapid growth; regenerative; scaffold; screening

Project Summary Back pain is the most common cause of disability worldwide with a lifetime prevalence of 80%. Intervertebral disc (IVD) degeneration is a major cause of low back pain. Currently, IVD degeneration is treated only symptomatically. Our ability to effectively treat disc disease is largely hampered by 1) an incomplete understanding of the biological processes of IVD development, function and disease; 2) The lack of an efficient and streamlined protocol for new drug discovery due to limited research platforms. To address the aforementioned problems, we propose to develop a novel microfluidic “disc-on-a-chip” organ culture platform tailored for mouse IVD. Our application-oriented microfluidic devices are designed to address key pathogenic factors, including biochemical (e.g. nutrients and inflammatory cytokines), mechanical and genetic aspects, contributing to disc degenerative diseases. Our short-term objective is to develop proof- of-concept microfluidic devices tailored for mouse IVD culture in multi-throughput (Aim 1) and physiologically simulated (Aim 2) manners and demonstrate respective application-oriented strategies for bridging in vitro IVD culture methodology with in vivo IVD biology/pathology and simulated drug evaluation. Our long-term goal is to establish a streamlined drug discovery protocol for new therapeutic and regenerative strategies using our integrated microfluidic mouse IVD culture platform. Microfluidic devices have been proven to be advantageous over their conventional counterparts in many aspects, since miniaturization, automation, and integration of fluidic control systems allow smaller reagent consumption, lower cost, shorter turnaround time, and higher throughput. Our proposed microfluidic mouse IVD culture devices will not only fill in the methodological blank of “disc-on-a-chip”, but also demonstrate a number of revolutionary benefits along the road to tackle disc degeneration: a) Culture media is continuously supplied/refreshed to mimick in vivo blood circulation, providing a unique platform to study the impacts of various biochemical factors such as oxygen, nutrients, cytokines, and growth factors on IVD metabolism; b) With multi- throughput platform, we can easily culture dozens of IVD samples, benefiting expedited drug discovery and evaluation protocols within a precisely defined microenvironment (Aim 1); c) Our physiologically simulated mechanical loading on mouse IVD empowers otherwise impossible cross-talking studies between genetic factor and mechanical stress (Aim 2); and d) Our micro-scale “disc-on-a-chip” device can be customized, commercialized, manufactured in mass production, and utilized by all research laboratories, shifting the paradigm of conventional disc research and meanwhile accelerating drug discovery processes in the battle against disc degeneration.

项目摘要 背痛是全世界最常见的拒绝性原因，终生患有80％。 椎间盘（IVD）变性是腰痛的主要原因。 只有症状。 了解IVD发育，功能和疾病的生物学过程； 2 由于研究平台有限，因此简化了新药物发现方案。 为了解决上述问题，我们建议开发一种新型的微流体“片段” 为小鼠IVD量身定制的器官文化平台。 解决关键的致病因素，包括生化（例如营养和炎性细胞因子），机械 和遗传方面，有助于椎间盘退化性疾病。 概念概念的微流体设备为小鼠IVD培养在多通量中的多种培养物（AIM 1）和生理学上 模拟（AIM 2）举止，并展示各自面向应用的策略的体外IVD 体内IVD生物学/病理学和模拟药物评估的培养方法。 使用我们的新治疗和再生策略建立简化的药物发现方案 集成的微流体小鼠IVD培养平台。 事实证明，微流体设备在其常规对应物中具有优势 许多方面，因为流体控制系统的微型化，自动化和集成允许较小的试剂 消费，较低的成本，较短的周转时间和更高的虽然。 培养设备将填充“片段片”的方法，但也证明了Anumber 沿途解决碟片变性的革命性利益：a）培养媒体融合了 提供/刷新以模仿体内血液循环，提供了一个独特的平台来研究各种的影响 IVD代谢上的氧气，营养素，细胞因子和生长因子等生化因素； 吞吐量平台，我们可以轻松文化数十个IVD样本，从而使加快药物发现和 精确定义的微环境中的评估方案（AIM 1）； 小鼠上的机械加载IVD征服遗传因素之间的不可能的不可能的交叉言论研究 和机械压力（AIM 2）和D）我们的微型“芯片盘”设备可以定制 商业化，在大规模生产中制造并被所有研究实验室使用，使他们转移 传统的识别搜索和同时在巴特勒的加速发现过程的范例 反对椎间盘堕落。