Engineering microsystems to recapitulate brain physiology on a chip

The structural and functional organization of the human brain consists of 52 regions with distinct cellular organization. In vitro models for normal and pathological states using isolated brain-regionspecific 3D engineered tissues fail to recapitulate information integration and/or transfer that arises from connectivity among neuroanatomical structures. Therefore, development of brain-on-a-chip microsystems must shift to multiple region neuron network designs to be relevant in brain functionality and deficit modeling. However, in vitro formation of multiregional networks on microdevices presents several challenges that we illustrate using a few neurological disorders; and we offer guidance, depending on objectives (HTS, disease modeling, etc.) for rational design of microfluidic systems and better emulation of in vivo conditions.