The Evolution of Technology-Driven In Vitro Models for Neurodegenerative Diseases

The alteration in the neural circuits of both central and peripheral nervous systems is closely related to the onset of neurodegenerative disorders (NDDs). Despite significant research efforts, the knowledge regarding NDD pathological processes, and the development of efficacious drugs are still limited due to the inability to access and reproduce the components of the nervous system and its intricate microenvironment. 2D culture systems are too simplistic to accurately represent the more complex and dynamic situation of cells in vivo and have therefore been surpassed by 3D systems. However, both models suffer from various limitations that can be overcome by employing two innovative technologies: organ-on-chip and 3D printing. In this review, an overview of the advantages and shortcomings of both microfluidic platforms and extracellular matrix-like biomaterials will be given. Then, the combination of microfluidics and hydrogels as a new synergistic approach to study neural disorders by analyzing the latest advances in 3D brain-on-chip for neurodegenerative research will be explored.