Blood-brain barrier (BBB)-on-a-chip: a promising breakthrough in brain disease research.

Abstract

The blood-brain barrier (BBB) represents a key challenge in developing brain-penetrating therapeutic molecules. BBB dysfunction is also associated with the onset and progression of various brain diseases. The BBB-on-a-chip (μBBB), an organ-on-chip technology, has emerged as a powerful <i>in vitro</i> platform that closely mimics the human BBB microenvironments. While the μBBB technology has seen wide application in the study of brain cancer, its utility in other brain disease models ("μBBB+") is less appreciated. Based on the advances of the μBBB technology and the evolution of <i>in vitro</i> models for brain diseases over the last decade, we propose the concept of a "μBBB+" system and summarize its major promising applications in pathological studies, personalized medical research, drug development, and multi-organ-on-chip approaches. We believe that such a sophisticated "μBBB+" system is a highly tunable and promising <i>in vitro</i> platform for further advancement of the understanding of brain diseases.