Potential applications of microfluidics based blood brain barrier (BBB)-on-chips for in vitro drug development.

• Microfluidic BBB chips composed of brain microvascular endothelial cells, pericytes, astrocytes and multifarious neurons can simulate the complex and dynamic 3D structure of human brain. • In vitro microfluidic BBB chips reproduce the mesh of the human brain anatomical structure and physiological function. • Brain on a chip has a great potential in exploring the mechanisms of CNS diseases and drug development. • Microfluidized BBB-related target organ chip platform can in vitro comprehensively investigate the dynamic process of brain-related multi-organ diseases. The human blood-brain barrier (BBB) is a complex multi-dimensional reticular barrier system composed of cerebral microvascular endothelial cells, pericytes, astrocytes and a variety of neurons. The conventional in vitro cell culture model fails to truly present the dynamic hemodynamics of BBB and the interaction between neurons. And it is even more impossible to explore brain-related multi-organ diseases, which brings huge obstacles to explore diseases of the central nervous system and the interaction between brain-related multi-organs, and evaluate drug efficacy. Miniaturized microfluidics based BBB chips are being commonly used to co-culture a variety of cells on a small-sized chip to construct a three-dimensional (3D) BBB or BBB-related organ disease models. By combining with other electrophysiological, biochemical sensors or equipment and imaging systems, it can in real time and quickly screen disease-related markers and evaluate drug efficacy. This review systematically summarized the research progress of in vitro BBB and BBB-related organ chips, and analyzed the obstacles of BBB models in depth. Parallelly combined with the current research trends and hot spots, we give the further improvement measures of microfluidic BBB chips. [ABSTRACT FROM AUTHOR]