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

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目前的一个项目是开发一种微流体装置，模仿血管化组织的关键特征。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为90%。有一个重要的新工具，以准确地模拟细胞屏障，如血管内皮，调节药物的运输到目标组织。能够支持内皮细胞和靶组织细胞的共培养系统，是改善体外细胞培养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的本质。因此，我们建议开发一种可以作为细胞屏障功能体外模型的微流控装置。****预期的装置将有两个平行的微流体通道，由多孔膜分开。选择具有生物相容性、可灭菌性和亲水性等特定表面特性的最佳材料是首要任务。特别是，通道应不粘附于细胞，而膜应粘附于细胞。如何有效地粘合/组装微流控通道、膜和设备的其他组件是第二个需要解决的问题。器件材料和制造工艺可能影响通道中的流动特性。流动特性很重要，因为流动所引入的剪切应力对培养细胞有影响。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。申请人在滑铁卢大学和CellScale实验室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。****

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.****