In-vitro engineered human cerebral tissues mimic pathological circuit disturbances in 3D

In-vitro modeling of brain network disorders such as epilepsy remains a major challenge. A critical step is to develop an experimental approach that enables recapitulation of in-vivo-like three-dimensional functional complexity while allowing local modulation of the neuronal networks. Here, by promoting matrix-supported active cell reaggregation, we engineered multiregional cerebral tissues with intact 3D neuronal networks and functional interconnectivity characteristic of brain networks. Furthermore, using a multi-chambered tissue-culture chip, we show that our separated but interconnected cerebral tissues can mimic neuropathological signatures such as the propagation of epileptiform discharges. A method is developed to engineer cerebral tissues with intact 3D neuronal networks, mimicking neuropathological signatures such as the propagation of epileptiform discharges, using a multi-chambered tissue culture chip.