Emerging Three‐Dimensional Integrated Systems for Biomimetic Neural In Vitro Cultures

Abstract

lial cells, and pericytes. [2] The intricate interconnections and spatial organization between neurons as well as between neuronal and non-neuronal cells enable the functional complexity and diversity of the brain, which ultimately generates motor and sensory function, as well as cognitive processes such as memory, learning, and emotions.Despite its critical functions, the brain has very limited ability to self-repair and regenerate upon neurological disease or injury. [3] The regeneration of damaged tissue in the brain after trauma is primarily impeded by glial scar formation and reactive astrocytes. [4] Conversely, neurodegenerative diseases are characterized by progressive dysfunction and loss of subpopulation of specialized cells such as dopaminergic neurons and oligodendrocytes. [5] Moreover, a number of changes occur in the brain extracellular matrix (bECM) in pathological situations, such as alterations in the expression of proteoglycans, protein aggregation, and amyloidosis during the progression of Alzheimer's disease (AD). [6] To investigate the mechanisms of regeneration and degeneration as well as those which regulate neural circuit formation, morphogenesis, and development, animal models have traditionally been the main research modality. However, these models have presented major challenges due to their genetic, biochemical, and metabolic differences to human physiology, along with the need for expensive and time-consuming protocols and associated ethical issues. In vitro models have been established as efficient alternatives, allowing recreating in vivolike micro-environments to study cellular differentiation, electrical activity, and their relationship to molecular signaling. Additionally, 3D in vitro models represent processes such as cell adhesion, migration, as well as of nutrient and metabolic waste transport in a more biomimetic context than conventional 2D culture. [7][8][9] Multidisciplinary approaches in the field of tissue engineering have emerged since the 1990s with the goal of fabricating biocompatible 3D bioengineered architectures composed of predefined compositions of cells, biomaterials, and biological factors. Ideally, these elements can be combined to generate biomimetic ECM formation and cellular phenotypes. [10][11][12] In parallel with technical advances in materials and fabrication techniques, the development of stem cell biology, and in particular the advent of 3D in vitro neural cultures have gained interest in recent years as promising biomimetic micro-environments which can regulate cell response to neural guidance cues. Several bioengineered technologies have been developed in combination with biomaterials to produce 3D models, such as scaffoldbased neural constructs, neurospheres, cerebral organoids, and brain-onchip devices. While the strategic selection of bioengineering approaches and associated biomaterials has opened a multitude of opportunities in building increasingly advanced neural tissues, technical limitations remain a challenge in modeling the complexity of ...

An electric-field-driven ferroelectric nanodomain structure and its multilevel data storage application

“…9–15 Ferroelectric-based solid-state synapses show promise for achieving a highly efficient biomimetic neural network. 6–20 The ferroelectric nanodomain structure is adjusted to control spike-timing-dependent plasticity or multilevel data storage in ferroelectric field effect transistors, memristors, and tunnel junctions. 6–20 As future biomimetic neural synaptic networks will consist of billions of ferroelectric material-based synapses, a clear understanding of the electric-field-driven ferroelectric nanodomain structure is necessary for their application.…”

“…[1][2][3][4][5][6][7][8] To address these challenges, researchers propose a biomimetic neural network that mimics the power-efficient and highly parallel computing of the human brain using artificial synapses. [8][9][10][11][12] These synapses reconfigure to facilitate learning through variable connection strength. [9][10][11][12][13][14][15] Ferroelectric-based solid-state synapses show promise for achieving a highly efficient biomimetic neural network.…”

“…[8][9][10][11][12] These synapses reconfigure to facilitate learning through variable connection strength. [9][10][11][12][13][14][15] Ferroelectric-based solid-state synapses show promise for achieving a highly efficient biomimetic neural network. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] The ferroelectric nanodomain structure is adjusted to control spike-timing-dependent plasticity or multilevel data storage in ferroelectric field effect transistors, memristors, and tunnel junctions.…”

“…[9][10][11][12][13][14][15] Ferroelectric-based solid-state synapses show promise for achieving a highly efficient biomimetic neural network. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] The ferroelectric nanodomain structure is adjusted to control spike-timing-dependent plasticity or multilevel data storage in ferroelectric field effect transistors, memristors, and tunnel junctions. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] As future biomimetic neural synaptic networks will consist of billions of ferroelectric material-based synapses, a clear understanding of the electric-field-driven ferroelectric nanodomain structure is necessary for their application.…”

Neuronal and glial cell co-culture organization and impedance spectroscopy on nanocolumnar TiN films for lab-on-a-chip devices

“…11 Great efforts have been made in recent years to bridge the gap between in vivo animal experiments and in vitro cell cultures, resulting in promising advances in biomimetic neural micro-environments, which mimic neural networks or structures found in the brain. 12,13 Such systems can offer great potential to study neural function, leading to the widespread field of brain-on-a-chip devices as, e.g., illustrated by Brofiga et al, 14 Maoz, 15 and Bang et al 16 However, the idea to recreate organs on chips does not end with brains, but rather extends to other organs such as lung, 17 liver, 18 kidney, 19 heart, 20 bone, 21 skin, 22 and many more. Thus, such organ-on-a-chip devices recapitulate the key features of the physiology of human organs.…”