In a myriad of developmental and degenerative brain diseases, characteristic pathological biomarkers are often associated with cerebral blood flow and vasculature. However, the relationship between vascular dysfunction and markers of brain disease is not well-defined. Additionally, it is difficult to deliver effective therapeutics to the brain due to the highly regulated blood-brain barrier (BBB) at the microvasculature interface of the brain. This Review first covers the need for modeling the BBB and the challenges of modeling the BBB. In vitro models of the BBB enable the study of the relationship between vascular dysfunction, BBB function, and disease progression and can serve as a platform to screen therapeutics. In particular, microfluidic-based in vitro BBB models are useful for studying brain vasculature as they support cell culture within the presence of continuous perfusion, which mirrors the in vivo flow and associated stress conditions in the brain. Early microfluidic models of the BBB created the most simplistic models possible that still displayed some functional aspects of the in vivo BBB. Therefore, this Review also discusses the emerging unique ways in which microfluidics in tandem with recent advancements in cell culture, biomaterials, and in vitro modeling can be used to develop more complex and physiologically relevant models of the BBB. Finally, we discuss the current and future state-of-the-art application of microfluidic BBB models for drug development and disease modeling, and the ongoing areas of needed innovation in this field.
Keywords: astrocytes; blood−brain barrier; endothelial cells; in vitro models; microenvironment; microfluidics; microphysiological systems; pericytes; vasculature.