BBB-on-a-Chip: Microfluidic Tools as an Alternative to In Vivo Experiments for Nanosafety Studies

Abstract

Nanoparticles (NPs) have attracted increasing interest due to their unique properties. However, their production and use have raised concerns about their unwanted effects on human health, particularly their potential to penetrate the blood-brain barrier (BBB) and their subsequent consequences on the central nervous system. Traditional in vivo models have been widely used to study NP interactions with the BBB, but these models often suffer from poor translatability to human physiology. This has driven the development of advanced in vitro models, such as BBB-on-chip systems, which offer a promising alternative for studying NP neurotoxicity and evaluating nanosafety. This chapter provides a comprehensive review of BBB-on-chip technology, including its design, biological integration, and application in nanosafety studies. The discussion highlights both the advantages and limitations of these models, such as the challenges in balancing tissue complexity with engineering constraints, the importance of dynamic conditions, and the need for improved sensorization. Despite these challenges, recent advances in the field are promising and BBB-on-chip models offer more and more reliable alternatives to animal testing.