Developments in micro-manufacture as well as biofabrication technologies are driving our ability to create complex tissue models such as ‘ organ-on-a-chip ’ devices. The complexity of neural tissue, however, requires precisely specific cellular connectivity across many neuronal populations, and thus there have been limited reports of complex ‘ brain-on-a-chip ’ technologies modelling specific cellular circuit function. Here we describe the development of a model of in vitro brain circuitry designed to accurately reproduce part of the complex circuitry involved in neurodegenerative diseases; using segregated co-culture of specific basal ganglia (BG) neuronal subtypes to model central nervous system circuitry. Lithographic methods and chemical modification were used to form structured micro-channels, which were populated by specifically cultured neuronal sub-types to represent parts of the inter-communicating neural circuit. Cell morphological assessment and immunostaining showed connectivity, which was supported by electrophysiology measurements. Electrical activity of cells was measured using patch-clamp, showing voltage dependant Na + and K + currents, and blocking of Na + current by TTX, and calcium imaging showing TTX-sensitive slow Ca 2+ oscillations resulting from action potentials. Monitoring cells across connected ports post-TTX addition demonstrated both upstream and downstream changes in activity, indicating network connectivity. The model developed herein provides a platform technology that could be used to better understand neurological function and dysfunction, contributing to a growing urgency for better treatments of neurodegenerative disease. We anticipate the use of this advancing technology for the assessment of pharmaceutical and cellular therapies as a means of pre-clinical assessment, and further for the advancement of neural engineering approaches for tissue engineering.

The increased prevalence of neurological diseases across the world has stimulated a great deal of research into the physiological and pathological brain, both at clinical and pre-clinical level. This has led to the development of many sophisticated tissue engineered neural models, presenting greater cellular complexity to better mimic the central nervous system niche environment. These have been developed with the ambition to improve pre-clinical assessment of pharma and cellular therapies, as well as better understand this tissue type and its function/dysfunction. This review covers the necessary considerations in in vitro model design, along with recent advances in 2Dculture systems, to 3D organoids and bio-artificial organs.