Unraveling brain diseases: the promise of brain-on-a-chip models

Brain disorders, encompassing a wide spectrum of neurological and psychiatric conditions, present a formidable challenge in modern medicine. Despite decades of research, the intricate complexity of the human brain still eludes comprehensive understanding, impeding the development of effective treatments. Recent advancements in microfluidics and tissue engineering have led to the development of innovative platforms known as "Brain-on-a-Chip" (BoC) i.e., advanced in vitro systems that aim to replicate the microenvironment of the brain with the highest possible fidelity. This technology offers a promising test-bed for studying brain disorders at the cellular and network levels, providing insights into disease mechanisms, drug screening, and, in perspective, the development of personalized therapeutic strategies. In this review, we provide an overview of the BoC models developed over the years to model and understand the onset and progression of some of the most severe neurological disorders in terms of incidence and debilitation (stroke, Parkinson's, Alzheimer's, and epilepsy). We also report some of the cutting-edge therapeutic approaches whose effects were evaluated by means of these technologies. Finally, we discuss potential challenges, and future perspectives of the BoC models.