Diseases of the central nervous system (CNS), including neurodegenerative disorders and brain cancers, represent one of the most pressing global health challenges, yet therapeutic development in this field remains remarkably inefficient. A major bottleneck is the blood–brain barrier (BBB), a highly selective and dynamic interface that tightly regulates molecular transport between the bloodstream and the brain parenchyma. Current preclinical models fail to reliably predict human BBB permeability and toxicity, leading to costly late-stage failures and extensive reliance on animal experimentation.
Traditional in vitro approaches lack 3D architecture, physiological flow, and real-time functional readouts. Conversely, in vivo animal models are expensive, ethically constrained, time-consuming, and often poorly predictive due to interspecies differences. As a result, there is a clear and unmet need for advanced human-relevant platforms that can faithfully reproduce BBB structure and function while enabling quantitative assessment of barrier integrity / model maturation and drug transport.
The main objective of the project BiSCUIT was to address this gap by developing sensorized, biomimetic 3D BBB-on-chip platform that combines real-scale vascular geometry, controlled microfluidic flow, and embedded with real-time monitoring of maturation and integrity through impedance-based measurements, such as trans-endothelial electrical resistance (TEER). This approach moves beyond endpoint assays, allowing continuous tracking of barrier dynamics under physiological and pathological conditions.
A further objective was to demonstrate the predictive power of the platform for drug delivery and nanomedicine, by assessing the transport and cellular interaction of therapeutic molecules and nanoparticles in conditions that closely mimic the human neurovascular unit. In the broader vision of the project, the BBB model is conceived as a modular component that can interface with advanced 3D disease models, including brain tumor cultures, enabling integrated studies of barrier crossing and downstream therapeutic efficacy.
The expected impact of the project is significant. Scientifically, it provided a robust and quantitative tool to investigate BBB physiology, dysfunction, and drug permeability with unprecedented spatiotemporal resolution. Technologically, it established a new generation of sensorized organ-on-chip systems that merge biomimetic microfabrication with real-time functional readouts. From a societal and economic perspective, the platform has the potential to reduce animal use in line with the 3Rs principle, lower preclinical development costs, and accelerate the translation of effective CNS therapies.
