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Review
, 23 (1), 100788

Biomimetic Materials and Their Utility in Modeling the 3-Dimensional Neural Environment

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Review

Biomimetic Materials and Their Utility in Modeling the 3-Dimensional Neural Environment

Arianna Cembran et al. iScience.

Abstract

The brain is a complex 3-dimensional structure, the organization of which provides a local environment that directly influences the survival, proliferation, differentiation, migration, and plasticity of neurons. To probe the effects of damage and disease on these cells, a synthetic environment is needed. Three-dimensional culturing of stem cells, neural progenitors, and neurons within fabricated biomaterials has demonstrated superior biomimetic properties over conventional 2-dimensional cultureware, offering direct recapitulation of both cell-cell and cell-extracellular matrix interactions. Within this review we address the benefits of deploying biomaterials as advanced cell culture tools capable of influencing neuronal fate and as in vitro models of the native in vivo microenvironment. We highlight recent and promising biomaterials approaches toward understanding neural network and their function relevant to neurodevelopment and provide our perspective on how these materials can be engineered and programmed to study both the healthy and diseased nervous system.

Keywords: Biomaterials; Cellular Neuroscience; Materials Science; Neuroscience.

Figures

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Figure 1
Figure 1
Cellular Organization and Differentiation in the Developing Neocortex Refer to the text for a description of processes of the neurogenesis. Figure reproduced with permission from Arai and Taverna (2017). Copyright © 2017 Arai and Taverna.
Figure 2
Figure 2
Cellular Organization within the Human SVZ (A) Coronal view of the human brain showing the lateral ventricle. (B) shows a schematic of the human SVZ that consists of four distinct layers. Refer to the text for an explanation of the zones. Figure reproduced with permission from Arias-Carrion (2008). Copyright © 2008 Arias-Carrión.
Figure 3
Figure 3
The Extracellular Matrix Composition The brain extracellular matrix consists of three major regions: the basal lamina, the perineural net, and the neural interstitial matrix. Image reproduced with permission from Kim et al. (2018). Copyright © 2018 Kim, Meade, Chen Feng, Rayyan, Hess-Dunning, and Ereifej.
Figure 4
Figure 4
Physical Structure Regulates Cell Behavior (1) Different fibers diameters impact on NSCs differentiation, with larger fibers favoring TUJ+ neuronal progenitors and small scaffold fibers preferencing oligodendrocyte progenitors. Image reproduced with permission from Christopherson et al. (2009). Copyright © 2008 Elsevier Ltd. All rights reserved. (2) SEM images confirm that cells on small fibers (panel d-f) present a stretched morphology similar to oligodendrocytes, whereas cells on larger fibers (panels i-j; g-h) show a similar morphology to neural progenitors, extending neurites preferentially along the scaffold fiber axis. Image reproduced with permission from Christopherson et al. (2009). Copyright © 2008 Elsevier Ltd. All rights reserved. (3) Surface topography controls cell shape: neurospheres plated on small PCL fiber mats coated with PDL (panels B and C) show migratory morphology (green arrow in panel C indicates extended processes), whereas neurospheres plated on larger PCL fiber mats, also coated with PDL, show less interaction (panels F and G) and spherical morphology (light blue arrow panel G). Small PCL fiber mats coated with laminin show bipolar morphology (panel E, white arrows) and large amount of extracellular matrix secretion (panel E, red arrows), and big PCL fiber mats induce migration of precursors out of neurospheres along the fibers. Image reproduced with permission from Czeisler et al. (2016). Copyright © 2016 Wiley Periodicals, Inc.
Figure 5
Figure 5
SAPs as Relevant Biomimetic Scaffolds (1) (A) Chemical structure of Fmoc-DDIKVAV. (B–E) Schematic of Fmoc-assembly process: π-β structure assembly resulting in nanofibers with the Fmoc groups in the core and the peptide sequence exposed to the outside. Figure reproduced with permission from Somaa et al. (2017). Copyright © 2017 The Authors. (2) The fibrous network can shear-encapsulate proteins such as BDNF to provide sustained delivery and at the same time structural and chemical support to cells. Image reproduced with permission from Nisbet et al., 2018. Copyright © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. (3) Treatment of primary cortical neurons with soluble BDNF and conditioned media from SAP-BDNF hydrogels shows elevated metabolic activity. Image reproduced with permission from Nisbet et al. (2018). Copyright © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. (4) BDNF functionalized SAPs can influence human NSCs implanted in vivo, resulting in increased survival and differentiation. Image reproduced with permission from Nisbet et al. (2018). Copyright © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Figure 6
Figure 6
A Brief Timeline of Key Milestone in Neural Stem Cells and Biomaterials Advances These contributions helped to set base for present advances in neural tissue engineering. NSCs discovery and isolation and the ability to engineer biocompatible materials suitable to the CNS have permitted merging neural stem cell therapies with 3D biomaterials encouraging repair and reconstruction within the CNS.
Figure 7
Figure 7
Nanotechnology Approaches to Direct Stem Cell-Based Neural Regeneration Nano-scaffolds offer great promise to generate tools suitable for neural applications. Soluble factors play an important role in directing the stem cells fate: to overcome challenges, advanced nanoparticle systems have been used to direct efficient delivery to control differentiation. Patterned surfaces have been utilized to guide neural differentiation and polarization. Image adapted with permission from Shah et al. (2016). Copyright © 2016, American Chemical Society.

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References

    1. Aboody K., Capela A., Niazi N., Stern J.H., Temple S. Translating stem cell studies to the clinic for CNS repair: current state of the art and the need for a Rosetta stone. Neuron. 2011;70:597–613. - PubMed
    1. Allen S.J., Watson J.J., Shoemark D.K., Barua N.U., Patel N.K. GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol. Ther. 2013;138:155–175. - PubMed
    1. Amunts K., Ebell C., Muller J., Telefont M., Knoll A., Lippert T. The Human Brain Project: creating a European research infrastructure to decode the human brain. Neuron. 2016;92:574–581. - PubMed
    1. Antoni D., Burckel H., Josset E., Noel G. Three-dimensional cell culture: a breakthrough in vivo. Int. J. Mol. Sci. 2015;16:5517–5527. - PMC - PubMed
    1. Arai Y., Taverna E. Neural progenitor cell polarity and cortical development. Front. Cell. Neurosci. 2017;11:384. - PMC - PubMed

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