Functional bioengineered models of the central nervous system

Abstract

The functional complexity of the central nervous system (CNS) is unparalleled in living organisms. Its nested cells, circuits and networks encode memories, move bodies and generate experiences. Neural tissues can be engineered to assemble model systems that recapitulate essential features of the CNS and to investigate neurodevelopment, delineate pathophysiology, improve regeneration and accelerate drug discovery. In this Review, we discuss essential structure–function relationships of the CNS and examine materials and design considerations, including composition, scale, complexity and maturation, of cell biology-based and engineering-based CNS models. We highlight region-specific CNS models that can emulate functions of the cerebral cortex, hippocampus, spinal cord, neural-X interfaces and other regions, and investigate a range of applications for CNS models, including fundamental and clinical research. We conclude with an outlook to future possibilities of CNS models, highlighting the engineering challenges that remain to be overcome.

Leveraging Biomaterial Platforms to Study Aging-Related Neural and Muscular Degeneration

“…In addition to the advantages offered by synthetic materials in terms of control over their mechanical properties, they also provide additional functions such as electroconductivity. An example of such a conductive material is poly(3,4-ethylenedioxythiophene) (PEDOT), which can electrically stimulate bioengineered neural tissues [182].…”

Self-Similarity and Spatial Periodicity in Cerebral Cortical Patterning: Structural Design Notes for Neural Tissue Architects

“…Designing unique neural architectures and examining emergent patterning phenomena as well as their functional correlates could reveal unique relationships. Indeed, in our recent reviews of advances in neural tissue engineering technologies [58] and their application as tools to explore cognition in vitro [11], we predicted that iterative brain tissues with alternative cytoarchitectures could represent toolkits to uncover mechanisms underlying learning, memory, decision-making, and consciousness.…”

The Multiple Realizability of Sentience in Living Systems and Beyond

“…However, we now know that an impressive variety of distinct brain morphologies can implement similar mental processes ranging from associative learning to context-dependent decision-making (Lefebvre and Sol, 2008). The same can be said of comparatively simple ganglia (Sarnat and Netsky, 2002), neural explants (Shultz et al, 2017), and tissue engineered neural cultures (Rouleau et al, 2021;Rouleau, 2022;Rouleau et al, 2023). Further support for the generalizability of cognitive function beyond brains, we have learned that several non-neural organisms display response patterns consistent with animal cognition (Boisseau et al, 2016;Smith-Ferguson and Beekman, 2020).…”