Translational Biology & Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON M5G 1M1, Canada.
Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
Lab Chip. 2024 Jun 25;24(13):3199-3225. doi: 10.1039/d3lc01027a.
Biological barriers such as the blood-brain barrier, skin, and intestinal mucosal barrier play key roles in homeostasis, disease physiology, and drug delivery - as such, it is important to create representative models to improve understanding of barrier biology and serve as tools for therapeutic development. Microfluidic cell culture and organ-on-a-chip (OOC) systems enable barrier modelling with greater physiological fidelity than conventional platforms by mimicking key environmental aspects such as fluid shear, accurate microscale dimensions, mechanical cues, extracellular matrix, and geometrically defined co-culture. As the prevalence of barrier-on-chip models increases, so does the importance of tools that can accurately assess barrier integrity and function without disturbing the carefully engineered microenvironment. In this review, we first provide a background on biological barriers and the physiological features that are emulated through barrier models. Then, we outline molecular permeability and electrical sensing barrier integrity assessment methods, and the related challenges specific to barrier-on-chip implementation. Finally, we discuss future directions in the field, as well important priorities to consider such as fabrication costs, standardization, and bridging gaps between disciplines and stakeholders.
生物屏障，如血脑屏障、皮肤和肠黏膜屏障，在维持体内平衡、疾病生理学和药物输送方面发挥着关键作用-因此，创建具有代表性的模型以提高对屏障生物学的理解并作为治疗开发的工具非常重要。微流控细胞培养和器官芯片 (OOC) 系统通过模拟关键环境方面，例如流体剪切、精确的微尺度尺寸、机械线索、细胞外基质和几何定义的共培养，比传统平台更能模拟生理相关性，从而实现屏障建模。随着芯片上屏障模型的普及，能够在不干扰精心设计的微环境的情况下准确评估屏障完整性和功能的工具的重要性也越来越大。在这篇综述中，我们首先提供了生物屏障的背景知识，以及通过屏障模型模拟的生理特征。然后，我们概述了分子通透性和电传感屏障完整性评估方法，以及与芯片上屏障实施相关的具体挑战。最后，我们讨论了该领域的未来发展方向，以及一些重要的优先事项，例如制造成本、标准化以及在学科和利益相关者之间架起桥梁。
