PDF(Sci-hub)
Abstract：
In recent years, the need for sophisticated human in vitro models for integrative biology has motivated the development of organ-on-a-chip platforms. Organ-on-a-chip devices are engineered to mimic the mechanical, biochemical and physiological properties of human organs; however, there are many important considerations when selecting or designing an appropriate device for investigating a specific scientific question. Building microfluidic Brain-on-a-Chip (BoC) models from the ground-up will allow for research questions to be answered more thoroughly in the brain research field, but the design of these devices requires several choices to be made throughout the design development phase. These considerations include the cell types, extracellular matrix (ECM) material(s), and perfusion/flow considerations. Choices made early in the design cycle will dictate the limitations of the device and influence the end-point results such as the permeability of the endothelial cell monolayer, and the expression of cell type-specific markers. To better understand why the engineering aspects of a microfluidic BoC need to be influenced by the desired biological environment, recent progress in microfluidic BoC technology is compared. This review focuses on perfusable blood-brain barrier (BBB) and neurovascular unit (NVU) models with discussions about the chip architecture, the ECM used, and how they relate to the in vivo human brain. With increased knowledge on how to make informed choices when selecting or designing BoC models, the scientific community will benefit from shorter development phases and platforms curated for their application.
摘要：
近年来,对复杂的人类体外综合生物学模型的需求推动了器官芯片平台的发展。芯片上的器官设备被设计成模仿机械，人体器官的生化和生理特性；然而，在选择或设计适当的设备来研究特定的科学问题时，有许多重要的考虑因素。从头开始构建微流控芯片大脑（BoC）模型将使研究问题在大脑研究领域得到更彻底的回答，但是这些设备的设计需要在整个设计开发阶段进行多种选择。这些考虑包括细胞类型，细胞外基质（ECM）材料，和灌注/流量考虑。在设计周期早期做出的选择将决定装置的局限性，并影响终点结果，如内皮细胞单层的通透性，和细胞类型特异性标志物的表达。为了更好地理解为什么微流控BoC的工程方面需要受到所需生物环境的影响，比较了微流体BoC技术的最新进展。这篇综述的重点是可灌注血脑屏障（BBB）和神经血管单元（NVU）模型，并讨论了芯片结构。使用的ECM，以及它们与体内人脑的关系。随着对如何在选择或设计BoC模型时做出明智选择的知识的增加，科学界将受益于较短的开发阶段和为其应用而策划的平台。
