Development of a co-culture microfluidic device that mimics vascularized tissues

开发模拟血管组织的共培养微流体装置

基本信息

批准号：
533713-2018
负责人：
Ren, Carolyn
金额：
$ 1.82万
依托单位：
University of Waterloo
依托单位国家：
加拿大
项目类别：
Engage Grants Program
财政年份：
2018
资助国家：
加拿大
起止时间：
2018-01-01 至 2019-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=663203
关键词：
Development co culture microfluidic device

项目摘要

CellScale develops, manufactures, and commercializes biomaterial mechanical test systems and bioreactors for tissue engineering applications. One of CellScale's current projects is to develop a microfluidic device that mimics the key characteristics of vascularized tissues. Accurately predicting in vivo drug response has been a challenge due to the lack of effective pre-clinical tools, resulting in a 90% false positive rate for compounds in clinical trials. There is a significant demand for new tools to accurately model cell barriers, such as blood vessel endothelium, that regulate the transport of drugs to target tissues. Co-culture systems that can support both endothelial and target tissue cells, represent a critical step towards improving the physiological relevance of in vitro cell culture. The inclusion of endothelial cells has been shown to more accurately replicate in vivo drug response, extend cell viability, and illuminate the nature of disease pathophysiology. Therefore, here we propose to develop a microfluidic device that can be used as an in vitro model of cell barrier function.****The intended device will have two parallel microfluidic channels separated by a porous membrane. Choosing optimal materials, which possess specific surface properties such as being biocompatible, sterilisable and hydrophilic, is the first task. In particular, the channels should be non-adhesive to cells while the membrane should be adhesive to cells. How to effectively bond/assemble the microfluidic channels, the membrane and other components of the device is the second issue to be addressed. The device material and manufacturing process may affect the flow characteristics in the channels. The flow characteristics are important because the shear stresses introduced by the flow have an impact of the cultured cells. Therefore, a third major task of this project will be to evaluate the impact on flow characteristics of various materials and assembly options. The integration of the expertise and facility available in the applicant's laboratory at the University of Waterloo and CellScale will ensure the success of the proposed co-culture microfluidic device.****

CellScale 开发、制造和商业化用于组织工程应用的生物材料机械测试系统和生物反应器。 CellScale 当前的项目之一是开发一种模仿血管组织关键特征的微流体装置。由于缺乏有效的临床前工具，准确预测体内药物反应一直是一个挑战，导致临床试验中化合物的假阳性率高达 90%。人们迫切需要新工具来准确模拟细胞屏障，例如调节药物向目标组织转运的血管内皮细胞。可以支持内皮细胞和靶组织细胞的共培养系统是提高体外细胞培养的生理相关性的关键一步。内皮细胞的加入已被证明可以更准确地复制体内药物反应、延长细胞活力并阐明疾病病理生理学的本质。因此，在这里我们建议开发一种可用作细胞屏障功能体外模型的微流体装置。****预期的装置将具有由多孔膜分隔的两个平行的微流体通道。选择具有特定表面特性（例如生物相容性、可消毒性和亲水性）的最佳材料是首要任务。特别是，通道应该不粘附细胞，而膜应该粘附细胞。如何有效地粘合/组装微流通道、膜和装置的其他部件是第二个要解决的问题。装置材料和制造工艺可能会影响通道中的流动特性。流动特性很重要，因为流动引入的剪切应力会对培养细胞产生影响。因此，该项目的第三个主要任务将是评估各种材料和装配选项对流动特性的影响。滑铁卢大学申请人实验室和 CellScale 的专业知识和设施的整合将确保所提议的共培养微流体装置的成功。****