Microphysiological Blood‐Brain Barrier Systems for Disease Modeling and Drug Development

The blood‐brain barrier (BBB) is a highly controlled microenvironment that regulates the interactions between cerebral blood and brain tissue. Due to its selectivity, many therapeutics targeting various neurological disorders are not able to penetrate into brain tissue. Pre‐clinical studies using animals and other in vitro platforms have not shown the ability to fully replicate the human BBB leading to the failure of a majority of therapeutics in clinical trials. However, recent innovations in vitro and ex vivo modeling called organs‐on‐chips have shown the potential to create more accurate disease models for improved drug development. These microfluidic platforms induce physiological stressors on cultured cells and are able to generate more physiologically accurate BBBs compared to previous in vitro models. In this review, different approaches to create BBBs‐on‐chips are explored alongside their application in modeling various neurological disorders and potential therapeutic efficacy. Additionally, organs‐on‐chips use in BBB drug delivery studies is discussed, and advances in linking brain organs‐on‐chips onto multiorgan platforms to mimic organ crosstalk are reviewed. This review explores the advancements in microphysiological blood‐brain barrier (BBB) systems, focusing on their application in disease modeling and drug development. Highlighting organ‐on‐a‐chip (OOC) technology, the review discusses the development of more accurate BBB models and their implications in brain disease modeling, therapeutics, and drug delivery. The integration of multiorgan platforms with organ crosstalk is also examined.