Implementation of blood-brain barrier on microfluidic chip: Recent advance and future prospects

The complex structure of the blood-brain barrier (BBB) hinders its modeling and the treatment of brain diseases. The microfluidic technology promotes the development of BBB-on-a-chip platforms, which can be used to reproduce the complex brain microenvironment and physiological reactions. Compared with traditional transwell technology, microfluidic BBB-on-a-chip shows great technical advantages in terms of flexible control of fluid shear stress in the chip and fabrication efficiency of the chip system, which can be enhanced by the development of lithography and three-dimensional (3D) printing. It is convenient to accurately monitor the dynamic changes of biochemical parameters of individual cells in the model by integrating an automatic super-resolution imaging sensing platform. In addition, biomaterials, especially hydrogels and conductive polymers, solve the limitations of microfluidic BBB-on-a-chip by compounding onto microfluidic chip to provide a 3D space and special performance on the microfluidic chip. The microfluidic BBB-on-a-chip promotes the development of basic research, including cell migration, mechanism exploration of neurodegenerative diseases, drug barrier permeability, SARS-CoV-2 pathology. This study summarizes the recent advances, challenges and future prospects of microfluidic BBB-on-a-chip, which can help to promote the development of personalized medicine and drug discovery.