Bioengineered functional brain-like cortical tissue

Abstract

The brain remains one of the most important but least understood tissues in our body, in part because of its complexity as well as the limitations associated with in vivo studies. Although simpler tissues have yielded to the emerging tools for in vitro 3D tissue cultures, functional brain-like tissues have not. We report the construction of complex functional 3D brain-like cortical tissue, maintained for months in vitro, formed from primary cortical neurons in modular 3D compartmentalized architectures with electrophysiological function. We show that, on injury, this brain-like tissue responds in vitro with biochemical and electrophysiological outcomes that mimic observations in vivo. This modular 3D brain-like tissue is capable of real-time nondestructive assessments, offering previously unidentified directions for studies of brain homeostasis and injury.electrophysiology | connectivity | silk | scaffold | traumatic brain injury

Toward in vitro models of brain structure and function

“…These in vitro models would also be invaluable test beds for drug-discovery investigations and in toxicology evaluations. In PNAS, Tang-Schomer et al (2) describe a promising model of a cortical tissue mimic and demonstrate its applications to a better understanding of response to TBI.…”

“…Several classes of in vitro models of the brain have been described (3), including acute preparations (or explants of CNS tissues), organotypic cultures or thin slices of CNS maintained for greater than 7 d, cerebral organoids (which can be formed from the self-organization of human pluripotent stem cells in 3D cultures) (3), and tissue-engineered constructs (2,4,5). Here we focus on the cell-based techniques for organoids and tissue-engineered constructs.…”

“…The composite model demonstrated an increase in neuronal clustering as well as improved cell viability when compared with gels. Tang-Schomer et al (2) suggest that these composites improve the transport of oxygen and nutrients compared with hydrogels alone, as the hydrogel structure may collapse because of gel degradation. The ability to sustain cellular activity will be important to the study of many disease states and potential response to treatment in future studies.…”

“…The authors also suggest the use of human iPSCs, as done in Lancaster et al (6) and Odawara et al (5), to transition from a rat to human system. One difficulty with the human iPSC approach is whether a more mature phenotype can be achieved; here the extended period of culture in Tang-Schomer et al (2) should aid in that goal. The use of human CNS cells would also make it more applicable to creating an in vitro model to verify work being done on the Brain Initiative now being investigated by the National Institutes of Health, the Defense Advanced Research Projects Agency, the National Science Foundation, and the European Union.…”

“…A tissueengineered model demonstrating complex CNS function is a distant goal! What TangSchomer et al (2) have done is to make a superior model emulating response to mechanical insults. This approach is clever, makes effective use of the basic tools of tissue engineering, and has direct applicability to an important human health issue (TBI).…”