The need for advanced three-dimensional neural models and developing enabling technologies

Merryweather, D. J.; Roach, Paul

doi:10.1557/mrc.2017.50

Cited by 7 publications

(14 citation statements)

References 99 publications

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“…According to the published data ( Table 1 ), the maximum growth of neurites was previously observed on oriented fibers 500–1000 nm in diameter. Structural components with the thickness of 500 nm turned out to be the most optimal, as assessed by the neurite growth rate and directionality [ 43 ]. At the same time, there’s hardly any published reports about the growth of neurons on scaffolds with ECM-like architecture and fiber diameter of ~10–300 nm.…”

Section: Discussionmentioning

confidence: 99%

ECM-Mimetic Nylon Nanofiber Scaffolds for Neurite Growth Guidance

2021

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Numerous nanostructured synthetic scaffolds mimicking the architecture of the natural extracellular matrix (ECM) have been described, but the polymeric nanofibers comprising the scaffold were substantially thicker than the natural collagen nanofibers of neural ECM. Here, we report neuron growth on electrospun scaffolds of nylon-4,6 fibers with an average diameter of 60 nm, which closely matches the diameter of collagen nanofibers of neural ECM, and compare their properties with the scaffolds of thicker 300 nm nanofibers. Previously unmodified nylon was not regarded as an independent nanostructured matrix for guided growth of neural cells; however, it is particularly useful for ultrathin nanofiber production. We demonstrate that, while both types of fibers stimulate directed growth of neuronal processes, ultrathin fibers are more efficient in promoting and accelerating neurite elongation. Both types of scaffolds also improved synaptogenesis and the formation of connections between hippocampal neurons; however, the mechanisms of interaction of neurites with the scaffolds were substantially different. While ultrathin fibers formed numerous weak immature β1-integrin-positive focal contacts localized over the entire cell surface, scaffolds of submicron fibers formed β1-integrin focal adhesions only on the cell soma. This indicates that the scaffold nanotopology can influence focal adhesion assembly involving various integrin subunits. The fabricated nanostructured scaffolds demonstrated high stability and resistance to biodegradation, as well as absence of toxic compound release after 1 month of incubation with live cells in vitro. Our results demonstrate the high potential of this novel type of nanofibers for clinical application as substrates facilitating regeneration of nervous tissue.

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Section: Discussionmentioning

confidence: 99%

ECM-Mimetic Nylon Nanofiber Scaffolds for Neurite Growth Guidance

2021

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“…One of the biggest drawbacks from the current work is the limited ability to replicate a humanized model. Many of the existing models rely heavily on the use of animal derived materials [Kose, 2017;Merryweather, 2017;Roach, 2008] which can be useful for biological computing applications but have limited scope within the area of drug testing or regenerative medicine. New approaches applying synthetic biology approaches to rapidly reprogram human pluripotent stem cells for the first time provide a robust and scalable source of functional human neurons [Pawlowski, 2017[Pawlowski, , 2013.…”

Section: Discussionmentioning

confidence: 99%

Mathematical Modeling of Neuronal Logic, Memory and Clocking Circuits

Lynch

Borresen

Roach

et al. 2020

Int. J. Bifurcation Chaos

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The differential equations used to model biological neurons and the chemical kinetics involved in synaptic excitation and inhibition have been well-established for a number of decades. For the first time, this paper presents mathematical and computational models of a neuronal binary oscillator half-adder, a neuronal Set-Reset (SR) flip-flop and a simple neuronal clocking circuit, which have all been shown to be noise resistant. In modern computers, the half-adder is the basic component to perform logic, the SR flip-flop is used to store memory and clocking circuits are used to synchronize components in parts of the computer. These novel circuits will provide the world with neuronal assays that can measure the functionality of the neurons and hence provide more information than is available with current technology. The authors are not proposing to build conventional computers with these components (they would be too slow to be practical) but the simple circuits could be used to measure the functionality of diseased circuits which are subjected to certain drugs. Neurological conditions research into Alzheimer’s disease, epilepsy and Parkinson’s disease, for example, would all benefit from this research. These assays for neuronal degradation could have major implications for the National Center for the Replacement, Refinement and Reduction of Animals in Research — otherwise known as the NC3R agenda.

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“…Notably, altered expression of matrix proteins such as CSPGs is associated with pathological states such as gliosis [26]. The ECM also contributes to mechanical properties such as stiffness, which is known to influence cellular behaviour [22,27]. Young's elastic modulus of brain tissue is estimated to be ∼ 0.1 to 10 kilopascals (kPa), with precise measurement hindered by regional variation and a lack of standardised measurement parameters [28][29][30].…”

Section: Created With Biorendercommentioning

confidence: 99%

“…These cells co-regulate critical processes such as neuronal network construction, synapse formation and wider spatial organisation [18][19][20][21]. Cells guide tissue formation by continually remodelling the extracellular matrix (ECM) to produce a biologically active macromolecular network that provides dynamic biochemical and physical support (Figure 1) [22][23][24]. The CNS ECM regulates a number of neuronal processes, with region-specific distribution of glycosaminoglycans (hyaluronan), proteoglycans (chondroitin sulfate proteoglycans (CSPGs), heparin sulfate proteoglycans (HSPGs), glycoproteins (laminin), and cell-matrix interaction modulates cellular behaviour via biochemical and mechanical stimuli-receptor interaction leading to induction of intracellular signalling cascades, with mechanosensing of matrix proteins often acting upon the internal cytoskeleton of the cell to evoke a biophysical response i.e.…”

Section: Introductionmentioning

confidence: 99%

Modelling the central nervous system: tissue engineering of the cellular microenvironment

Walczak

Esteban

Bassett

et al. 2021

Emerging Topics in Life Sciences

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With the increasing prevalence of neurodegenerative diseases, improved models of the central nervous system (CNS) will improve our understanding of neurophysiology and pathogenesis, whilst enabling exploration of novel therapeutics. Studies of brain physiology have largely been carried out using in vivo models, ex vivo brain slices or primary cell culture from rodents. Whilst these models have provided great insight into complex interactions between brain cell types, key differences remain between human and rodent brains, such as degree of cortical complexity. Unfortunately, comparative models of human brain tissue are lacking. The development of induced Pluripotent Stem Cells (iPSCs) has accelerated advancement within the field of in vitro tissue modelling. However, despite generating accurate cellular representations of cortical development and disease, two-dimensional (2D) iPSC-derived cultures lack an entire dimension of environmental information on structure, migration, polarity, neuronal circuitry and spatiotemporal organisation of cells. As such, researchers look to tissue engineering in order to develop advanced biomaterials and culture systems capable of providing necessary cues for guiding cell fates, to construct in vitro model systems with increased biological relevance. This review highlights experimental methods for engineering of in vitro culture systems to recapitulate the complexity of the CNS with consideration given to previously unexploited biophysical cues within the cellular microenvironment.

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The need for advanced three-dimensional neural models and developing enabling technologies

Abstract: Abstract

Cited by 7 publications

References 99 publications

ECM-Mimetic Nylon Nanofiber Scaffolds for Neurite Growth Guidance

ECM-Mimetic Nylon Nanofiber Scaffolds for Neurite Growth Guidance

Mathematical Modeling of Neuronal Logic, Memory and Clocking Circuits

Modelling the central nervous system: tissue engineering of the cellular microenvironment

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