Organ-on-chip models for blood–brain barrier permeability studies

In the context of global aging, neurodegenerative diseases, brain cancers, and other brain-related disorders are receiving increased attentions. The blood–brain barrier (BBB) maintains the brain homeostasis; and BBB dysfunction, such as increased barrier permeability, plays an important role in the onset and progression of various brain diseases. The BBB has long been regarded as a bottleneck in drug development for brain diseases, with more than 90% of potential drugs are restricted to cross the BBB and reach their cerebral targets. Currently, two-dimensional cell culture and animal models—commonly used in brain pathology research and drug development—are lacking a high degree human physiological correlation. In contrast, novel organ-on-a-chip models based on cell biology, microfluidic technology, and micro-nano manufacturing technology have the advantages of three-dimensional, complex tissue culture, high human physiological correlation, and high-throughput screening. Organ-on-chips models have become a popular and emerging in vitro model for BBB research (i.e., BBB-on-a-chip, μBBB), especially for brain diseases modeling. Herein, in this chapter, we first provide an overview of the composition and the importance of the BBB in physiological functions. We then highlight several different μBBB designs, including the techniques used to measure BBB permeability on chip. Finally, we discuss the μBBB applications and potential breakthrough directions of utilizing such novel systems for brain disease research.