Lab-on-a-chip models of the blood-brain barrier: evolution, problems, perspectives

A great progress has been made in the development and use of lab-on-a-chip devices to model and study the blood-brain barrier (BBB) in the last decade. We present the main types of BBB-on-chip models and their use for the investigation of BBB physiology, drug and nanoparticle transport, toxicology and pathology. The selection of the appropriate cell types to be integrated into BBB-on-chip devices is discussed, as this greatly impacts the physiological relevance and translatability of findings. We identify knowledge gaps, neglected engineering and cell biological aspects and point out problems and contradictions in the literature of BBB-on-chip models, and suggest areas for further studies to progress this highly interdisciplinary field. BBB-on-chip models have an exceptional potential as predictive tools and alternatives of animal experiments in basic and preclinical research. To exploit the full potential of this technique expertise from materials science, bioengineering as well as stem cell and vascular/BBB biology is necessary. There is a need for better integration of these diverse disciplines that can only be achieved by setting clear parameters for characterizing both the chip and the BBB model parts technically and functionally.