Skip to main content

Neuronal Cultures and Nanomaterials

  • Chapter
  • First Online:
In Vitro Neuronal Networks

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 22))

Abstract

In recent years, the scientific community has witnessed an exponential increase in the use of nanomaterials for biomedical applications. In particular, the interest of graphene and graphene-based materials has rapidly risen in the neuroscience field due to the properties of this material, such as high conductivity, transparency and flexibility. As for any new material that aims to play a role in the biomedical area, a fundamental aspect is the evaluation of its toxicity, which strongly depends on material composition, chemical functionalization and dimensions. Furthermore, a wide variety of three-dimensional scaffolds have also started to be exploited as a substrate for tissue engineering. In this application, the topography is probably the most relevant amongst the various properties of the different materials, as it may allow to instruct and interrogate neural networks, as well as to drive neural growth and differentiation.

This chapter discusses the in vitro approaches, ranging from microscopy analysis to physiology measurements, to investigate the interaction of graphene with the central nervous system. Moreover, the in vitro use of three-dimensional scaffolds is described and commented.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abbott, N. J., Ronnback, L., & Hansson, E. (2006). Astrocyte-endothelial interactions at the blood-brain barrier. Nature Reviews. Neuroscience, 7(1), 41–53.

    Article  CAS  PubMed  Google Scholar 

  • Aijaz, S., Balda, M. S., & Matter, K. (2006). Tight junctions: Molecular architecture and function. International Review of Cytology, 248, 261–298.

    Article  CAS  PubMed  Google Scholar 

  • Akhavan, O., Ghaderi, E., & Akhavan, A. (2012). Size-dependent genotoxicity of graphene nanoplatelets in human stem cells. Biomaterials, 33(32), 8017–8025.

    Article  CAS  PubMed  Google Scholar 

  • Allen, T. M., & Cullis, P. R. (2004). Drug delivery systems: Entering the mainstream. Science, 303(5665), 1818–1822.

    Article  CAS  PubMed  Google Scholar 

  • Aota, S., Nomizu, M., & Yamada, K. M. (1994). The short amino acid sequence Pro-His-Ser-Arg-Asn in human fibronectin enhances cell-adhesive function. The Journal of Biological Chemistry, 269(40), 24756–24761.

    CAS  PubMed  Google Scholar 

  • Bang, O. Y., Lee, J. S., Lee, P. H., & Lee, G. (2005). Autologous mesenchymal stem cell transplantation in stroke patients. Annals of Neurology, 57(6), 874–882.

    Article  PubMed  Google Scholar 

  • Barros, C. S., Franco, S. J., & Muller, U. (2011). Extracellular matrix: Functions in the nervous system. Cold Spring Harbor Perspectives in Biology, 3(1), a005108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beuckmann, C. T., & Galla, H.-J. (1998). Tissue culture of brain endothelial cells—induction of blood-brain barrier properties by brain factors. In W. M. Pardridge (Ed.), Introduction to the blood-brain barrier. Cambridge: Cambridge University Press.

    Google Scholar 

  • Bhabra, G., Sood, A., Fisher, B., Cartwright, L., Saunders, M., Evans, W. H., et al. (2009). Nanoparticles can cause DNA damage across a cellular barrier. Nature Nanotechnology, 4(12), 876–883.

    Article  CAS  PubMed  Google Scholar 

  • Bianco, A. (2013). Graphene: Safe or toxic? The two faces of the medal. Angewandte Chemie, 52(19), 4986–4997.

    Article  CAS  PubMed  Google Scholar 

  • Bicker, J., Alves, G., Fortuna, A., & Falcao, A. (2014). Blood-brain barrier models and their relevance for a successful development of CNS drug delivery systems: A review. European Journal of Pharmaceutics and Biopharmaceutics, 87(3), 409–432.

    Article  CAS  PubMed  Google Scholar 

  • Booth, R., & Kim, H. (2012). Characterization of a microfluidic in vitro model of the blood-brain barrier (muBBB). Lab on a Chip, 12(10), 1784–1792.

    Article  CAS  PubMed  Google Scholar 

  • Bramini, M., Alberini, G., Colombo, E., Chiacchiaretta, M., DiFrancesco, M. L., Maya-Vetencourt, J. F., et al. (2018). Interfacing graphene-based materials with neural cells. Frontiers in Systems Neuroscience, 12, 12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bramini, M., Sacchetti, S., Armirotti, A., Rocchi, A., Vazquez, E., Leon Castellanos, V., et al. (2016). Graphene oxide nanosheets disrupt lipid composition, Ca(2+) homeostasis, and synaptic transmission in primary cortical neurons. ACS Nano, 10(7), 7154–7171.

    Article  CAS  PubMed  Google Scholar 

  • Bramini, M., Ye, D., Hallerbach, A., Nic Raghnaill, M., Salvati, A., Aberg, C., et al. (2014). Imaging approach to mechanistic study of nanoparticle interactions with the blood-brain barrier. ACS Nano, 8(5), 4304–4312.

    Article  CAS  PubMed  Google Scholar 

  • Bussy, C., & Kostarelos, K. (2017). Culture media critically influence graphene oxide effects on plasma membranes. Chem, 2(3), 322–323.

    Article  CAS  Google Scholar 

  • Butt, A. M., & Jones, H. C. (1992). Effect of histamine and antagonists on electrical resistance across the blood-brain barrier in rat brain-surface microvessels. Brain Research, 569(1), 100–105.

    Article  CAS  PubMed  Google Scholar 

  • Callahan, L. A., Xie, S., Barker, I. A., Zheng, J., Reneker, D. H., Dove, A. P., et al. (2013). Directed differentiation and neurite extension of mouse embryonic stem cell on aligned poly(lactide) nanofibers functionalized with YIGSR peptide. Biomaterials, 34(36), 9089–9095.

    Article  CAS  PubMed  Google Scholar 

  • Cesca, F., Limongi, T., Accardo, A., Rocchi, A., Orlando, M., Shalabaeva, V., et al. (2014). Fabrication of biocompatible free-standing nanopatterned films for primary neuronal cultures. RSC Advances, 4(86), 45696–45702.

    Article  CAS  Google Scholar 

  • Chen, G. Y., Chen, C. L., Tuan, H. Y., Yuan, P. X., Li, K. C., Yang, H. J., et al. (2014). Graphene oxide triggers toll-like receptors/autophagy responses in vitro and inhibits tumor growth in vivo. Advanced Healthcare Materials, 3(9), 1486–1495.

    Article  CAS  PubMed  Google Scholar 

  • Chen, Y., Star, A., & Vidal, S. (2013). Sweet carbon nanostructures: Carbohydrate conjugates with carbon nanotubes and graphene and their applications. Chemical Society Reviews, 42(11), 4532–4542.

    Article  CAS  PubMed  Google Scholar 

  • Cheng, C. L., Li, S., Thomas, A., Kotov, A. N., & Haag, R. (2016). Functional graphene nanomaterials based architectures: Biointeractions, fabrications, and emerging biological applications. Chemical Reviews, 117(3), 1826–1914.

    Article  CAS  Google Scholar 

  • Chiacchiaretta, M., Bramini, M., Rocchi, A., Armirotti, A., Giordano, E., Vázquez, E., et al. (2018, Aug 15). Graphene oxide upregulates the homeostatic functions of primary astrocytes and modulates astrocyte-to-neuron communication. Nano Letters. https://doi.org/10.1021/acs.nanolett.8b02487

  • Chong, Y., Ge, C., Yang, Z., Garate, J. A., Gu, Z., Weber, J. K., et al. (2015). Reduced cytotoxicity of graphene nanosheets mediated by blood-protein coating. ACS Nano, 9(6), 5713–5724.

    Article  CAS  PubMed  Google Scholar 

  • Christopherson, G. T., Song, H., & Mao, H. Q. (2009). The influence of fiber diameter of electrospun substrates on neural stem cell differentiation and proliferation. Biomaterials, 30(4), 556–564.

    Article  CAS  PubMed  Google Scholar 

  • Chua, J. S., Chng, C. P., Moe, A. A., Tann, J. Y., Goh, E. L., Chiam, K. H., et al. (2014). Extending neurites sense the depth of the underlying topography during neuronal differentiation and contact guidance. Biomaterials, 35(27), 7750–7761.

    Article  CAS  PubMed  Google Scholar 

  • Corey, J. M., Gertz, C. C., Wang, B. S., Birrell, L. K., Johnson, S. L., Martin, D. C., et al. (2008). The design of electrospun PLLA nanofiber scaffolds compatible with serum-free growth of primary motor and sensory neurons. Acta Biomaterialia, 4(4), 863–875.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Corey, J. M., Lin, D. Y., Mycek, K. B., Chen, Q., Samuel, S., Feldman, E. L., et al. (2007). Aligned electrospun nanofibers specify the direction of dorsal root ganglia neurite growth. Journal of Biomedical Materials Research. Part A, 83(3), 636–645.

    Article  CAS  PubMed  Google Scholar 

  • Crone, C., & Olesen, S. P. (1982). Electrical resistance of brain microvascular endothelium. Brain Research, 241(1), 49–55.

    Article  CAS  PubMed  Google Scholar 

  • Cucullo, L., Hossain, M., Puvenna, V., Marchi, N., & Janigro, D. (2011). The role of shear stress in blood-brain barrier endothelial physiology. BMC Neuroscience, 12, 40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Defterali, C., Verdejo, R., Majeed, S., Boschetti-de-Fierro, A., Mendez-Gomez, H. R., Diaz-Guerra, E., et al. (2016). In vitro evaluation of biocompatibility of uncoated thermally reduced graphene and carbon nanotube-loaded PVDF membranes with adult neural stem cell-derived neurons and glia. Frontiers in Bioengineering and Biotechnology, 4, 94.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dell’Orco, D., Lundqvist, M., Oslakovic, C., Cedervall, T., & Linse, S. (2010). Modeling the time evolution of the nanoparticle-protein corona in a body fluid. PLoS One, 5(6), e10949.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dityatev, A., & Schachner, M. (2003). Extracellular matrix molecules and synaptic plasticity. Nature Reviews. Neuroscience, 4(6), 456–468.

    Article  CAS  PubMed  Google Scholar 

  • Dityatev, A., Seidenbecher, C. I., & Schachner, M. (2010). Compartmentalization from the outside: The extracellular matrix and functional microdomains in the brain. Trends in Neurosciences, 33(11), 503–512.

    Article  CAS  PubMed  Google Scholar 

  • Donaldson, K., Aitken, R., Tran, L., Stone, V., Duffin, R., Forrest, G., et al. (2006). Carbon nanotubes: A review of their properties in relation to pulmonary toxicology and workplace safety. Toxicological Sciences, 92(1), 5–22.

    Article  CAS  PubMed  Google Scholar 

  • Erni, R., Rossell, M. D., Kisielowski, C., & Dahmen, U. (2009). Atomic-resolution imaging with a sub-50-pm electron probe. Physical Review Letters, 102(9), 096101.

    Article  CAS  PubMed  Google Scholar 

  • European Commission PH. (2006). Nanotechnologies. http://ec.europa.eu/health/scientific_committees/opinions_layman/fr/nanotechnologies/l-3/1-introduction.htm

  • Fahmi, T., Branch, D., Nima, Z. A., Jang, D. S., Savenka, A. V., Biris, A. S., et al. (2017). Mechanism of graphene-induced cytotoxicity: Role of endonucleases. Journal of Applied Toxicology, 37(11), 1325–1332.

    Article  CAS  PubMed  Google Scholar 

  • Fitch, M. T., & Silver, J. (2008). CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure. Experimental Neurology, 209(2), 294–301.

    Article  CAS  PubMed  Google Scholar 

  • Gaffaney, J. D., Dunning, F. M., Wang, Z., Hui, E., & Chapman, E. R. (2008). Synaptotagmin C2B domain regulates Ca2+-triggered fusion in vitro: Critical residues revealed by scanning alanine mutagenesis. The Journal of Biological Chemistry, 283(46), 31763–31775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gall, C. M., & Lynch, G. (2004). Integrins, synaptic plasticity and epileptogenesis. Advances in Experimental Medicine and Biology, 548, 12–33.

    Article  CAS  PubMed  Google Scholar 

  • Georgakilas, V., Tiwari, J. N., Kemp, K. C., Perman, J. A., Bourlinos, A. B., Kim, K. S., et al. (2016). Noncovalent functionalization of graphene and graphene oxide for energy materials, biosensing, catalytic, and biomedical applications. Chemical Reviews, 116(9), 5464–5519.

    Article  CAS  PubMed  Google Scholar 

  • Goenka, S., Sant, V., & Sant, S. (2014). Graphene-based nanomaterials for drug delivery and tissue engineering. Journal of Controlled Release, 173, 75–88.

    Article  CAS  PubMed  Google Scholar 

  • Gottipati, M. K., Bekyarova, E., Brenner, M., Haddon, R. C., & Parpura, V. (2014). Changes in the morphology and proliferation of astrocytes induced by two modalities of chemically functionalized single-walled carbon nanotubes are differentially mediated by glial fibrillary acidic protein. Nano Letters, 14(7), 3720–3727.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halberstadt, C., Emerich, D. F., & Gonsalves, K. (2006). Combining cell therapy and nanotechnology. Expert Opinion on Biological Therapy, 6(10), 971–981.

    Article  CAS  PubMed  Google Scholar 

  • Hubatsch, I., Ragnarsson, E. G., & Artursson, P. (2007). Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers. Nature Protocols, 2(9), 2111–2119.

    Article  CAS  PubMed  Google Scholar 

  • Hynes, R. O. (2009). The extracellular matrix: Not just pretty fibrils. Science, 326(5957), 1216–1219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johansson, F., Carlberg, P., Danielsen, N., Montelius, L., & Kanje, M. (2006). Axonal outgrowth on nano-imprinted patterns. Biomaterials, 27(8), 1251–1258.

    Article  CAS  PubMed  Google Scholar 

  • John, A. A., Subramanian, A. P., Vellayappan, M. V., Balaji, A., Mohandas, H., & Jaganathan, S. K. (2015). Carbon nanotubes and graphene as emerging candidates in neuroregeneration and neurodrug delivery. International Journal of Nanomedicine, 10, 4267–4277.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ketabi-Kiyanvash, N., Herold-Mende, C., Kashfi, F., Caldeira, S., Tommasino, M., Haefeli, W. E., et al. (2007). NKIM-6, a new immortalized human brain capillary endothelial cell line with conserved endothelial characteristics. Cell and Tissue Research, 328(1), 19–29.

    Article  CAS  PubMed  Google Scholar 

  • Khan, S. P., Auner, G. G., & Newaz, G. M. (2005). Influence of nanoscale surface roughness on neural cell attachment on silicon. Nanomedicine, 1(2), 125–129.

    Article  CAS  PubMed  Google Scholar 

  • Krause, G., Winkler, L., Mueller, S. L., Haseloff, R. F., Piontek, J., & Blasig, I. E. (2008). Structure and function of claudins. Biochimica et Biophysica Acta, 1778(3), 631–645.

    Article  CAS  PubMed  Google Scholar 

  • Kubinova, S., Horak, D., Kozubenko, N., Vanecek, V., Proks, V., Price, J., et al. (2010). The use of superporous Ac-CGGASIKVAVS-OH-modified PHEMA scaffolds to promote cell adhesion and the differentiation of human fetal neural precursors. Biomaterials, 31(23), 5966–5975.

    Article  CAS  PubMed  Google Scholar 

  • Kurapati, R., Backes, C., Menard-Moyon, C., Coleman, J. N., & Bianco, A. (2016). White graphene undergoes peroxidase degradation. Angewandte Chemie, 55(18), 5506–5511.

    Article  CAS  PubMed  Google Scholar 

  • Kusch-Poddar, M., Drewe, J., Fux, I., & Gutmann, H. (2005). Evaluation of the immortalized human brain capillary endothelial cell line BB19 as a human cell culture model for the blood-brain barrier. Brain Research, 1064(1-2), 21–31.

    Article  CAS  PubMed  Google Scholar 

  • Lerou, P. H., & Daley, G. Q. (2005). Therapeutic potential of embryonic stem cells. Blood Reviews, 19(6), 321–331.

    Article  PubMed  Google Scholar 

  • Li, C. W., Davis, B., Shea, J., Sant, H., Gale, B. K., & Agarwal, J. (2018). Optimization of micropatterned poly(lactic-co-glycolic acid) films for enhancing dorsal root ganglion cell orientation and extension. Neural Regeneration Research, 13(1), 105–111.

    Article  PubMed  PubMed Central  Google Scholar 

  • Li, X., Liu, X., Josey, B., Chou, C. J., Tan, Y., Zhang, N., et al. (2014). Short laminin peptide for improved neural stem cell growth. Stem Cells Translational Medicine, 3(5), 662–670.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liao, K. H., Lin, Y. S., Macosko, C. W., & Haynes, C. L. (2011). Cytotoxicity of graphene oxide and graphene in human erythrocytes and skin fibroblasts. ACS Applied Materials and Interfaces, 3(7), 2607–2615.

    Article  CAS  PubMed  Google Scholar 

  • Lietz, M., Dreesmann, L., Hoss, M., Oberhoffner, S., & Schlosshauer, B. (2006). Neuro tissue engineering of glial nerve guides and the impact of different cell types. Biomaterials, 27(8), 1425–1436.

    Article  CAS  PubMed  Google Scholar 

  • Lim, M. H., Jeung, I. C., Jeong, J., Yoon, S. J., Lee, S. H., Park, J., et al. (2016). Graphene oxide induces apoptotic cell death in endothelial cells by activating autophagy via calcium-dependent phosphorylation of c-Jun N-terminal kinases. Acta Biomaterialia, 46, 191–203.

    Article  CAS  PubMed  Google Scholar 

  • Limongi, T., Cesca, F., Gentile, F., Marotta, R., Ruffilli, R., Barberis, A., et al. (2013). Nanostructured superhydrophobic substrates trigger the development of 3D neuronal networks. Small, 9(3), 402–412.

    Article  CAS  PubMed  Google Scholar 

  • Limongi, T., Rocchi, A., Cesca, F., Tan, H., Miele, E., Giugni, A., et al. (2018). Delivery of brain-derived neurotrophic factor by 3D biocompatible polymeric scaffolds for neural tissue engineering and neuronal regeneration. Molecular Neurobiology, 55(12), 8788–8798.

    Article  CAS  PubMed  Google Scholar 

  • Liu, G., Shen, H., Mao, J., Zhang, L., Jiang, Z., Sun, T., et al. (2013). Transferrin modified graphene oxide for glioma-targeted drug delivery: In vitro and in vivo evaluations. ACS Applied Materials and Interfaces, 5(15), 6909–6914.

    Article  CAS  PubMed  Google Scholar 

  • Manzoli, F. A., Barbieri, M., & Carinci, P. (1969). Lipid composition of brain synaptic vesicle fraction. Acta Anatomica Supplementum (Basel), (56), 283–292.

    Google Scholar 

  • Mattei, T. A., & Rehman, A. A. (2014). Technological developments and future perspectives on graphene-based metamaterials: A primer for neurosurgeons. Neurosurgery, 74(5), 499–516. Discussion.

    Article  PubMed  Google Scholar 

  • McCallion, C., Burthem, J., Rees-Unwin, K., Golovanov, A., & Pluen, A. (2016). Graphene in therapeutics delivery: Problems, solutions and future opportunities. European Journal of Pharmaceutics and Biopharmaceutics, 104, 235–250.

    Article  CAS  PubMed  Google Scholar 

  • Mendonca, M. C., Soares, E. S., de Jesus, M. B., Ceragioli, H. J., Batista, A. G., Nyul-Toth, A., et al. (2016b). PEGylation of reduced graphene oxide induces toxicity in cells of the blood-brain barrier: An in vitro and in vivo study. Molecular Pharmaceutics, 13(11), 3913–3924.

    Article  CAS  PubMed  Google Scholar 

  • Mendonca, M. C., Soares, E. S., de Jesus, M. B., Ceragioli, H. J., Irazusta, S. P., Batista, A. G., et al. (2016a). Reduced graphene oxide: Nanotoxicological profile in rats. J Nanobiotechnology., 14(1), 53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Micholt, L., Gartner, A., Prodanov, D., Braeken, D., Dotti, C. G., & Bartic, C. (2013). Substrate topography determines neuronal polarization and growth in vitro. PLoS One, 8(6), e66170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller, C., Jeftinija, S., & Mallapragada, S. (2002). Synergistic effects of physical and chemical guidance cues on neurite alignment and outgrowth on biodegradable polymer substrates. Tissue Engineering, 8(3), 367–378.

    Article  CAS  PubMed  Google Scholar 

  • Mittal, S., Kumar, V., Dhiman, N., Chauhan, L. K., Pasricha, R., & Pandey, A. K. (2016). Physico-chemical properties based differential toxicity of graphene oxide/reduced graphene oxide in human lung cells mediated through oxidative stress. Scientific Reports, 6, 39548.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morita, S. Y., Shirakawa, S., Kobayashi, Y., Nakamura, K., Teraoka, R., Kitagawa, S., et al. (2012). Enzymatic measurement of phosphatidylserine in cultured cells. Journal of Lipid Research, 53(2), 325–330.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mu, Q., Su, G., Li, L., Gilbertson, B. O., Yu, L. H., Zhang, Q., et al. (2012). Size-dependent cell uptake of protein-coated graphene oxide nanosheets. ACS Applied Materials and Interfaces, 4(4), 2259–2266.

    Article  CAS  PubMed  Google Scholar 

  • Murphy, D. D., Cole, N. B., Greenberger, V., & Segal, M. (1998). Estradiol increases dendritic spine density by reducing GABA neurotransmission in hippocampal neurons. The Journal of Neuroscience, 18(7), 2550–2559.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagahara, A. H., & Tuszynski, M. H. (2011). Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nature Reviews. Drug Discovery, 10(3), 209–219.

    Article  CAS  PubMed  Google Scholar 

  • Nakagawa, S., Deli, M. A., Kawaguchi, H., Shimizudani, T., Shimono, T., Kittel, A., et al. (2009). A new blood-brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes. Neurochemistry International, 54(3-4), 253–263.

    Article  CAS  PubMed  Google Scholar 

  • Navone, S. E., Marfia, G., Invernici, G., Cristini, S., Nava, S., Balbi, S., et al. (2013). Isolation and expansion of human and mouse brain microvascular endothelial cells. Nature Protocols, 8(9), 1680–1693.

    Article  CAS  PubMed  Google Scholar 

  • Nelson, G. J., & Freeman, N. K. (1960). The phospholipid and phospholipid fatty acid composition of human serum lipoprotein fractions. The Journal of Biological Chemistry, 235, 578–583.

    CAS  PubMed  Google Scholar 

  • Ogunshola, O. O. (2011). In vitro modeling of the blood-brain barrier: Simplicity versus complexity. Current Pharmaceutical Design, 17(26), 2755–2761.

    Article  CAS  PubMed  Google Scholar 

  • Ohno, K., Pettigrew, K. D., & Rapoport, S. I. (1978). Lower limits of cerebrovascular permeability to nonelectrolytes in the conscious rat. The American Journal of Physiology, 235(3), H299–H307.

    CAS  PubMed  Google Scholar 

  • Omidi, Y., Campbell, L., Barar, J., Connell, D., Akhtar, S., & Gumbleton, M. (2003). Evaluation of the immortalised mouse brain capillary endothelial cell line, b.End3, as an in vitro blood-brain barrier model for drug uptake and transport studies. Brain Research, 990(1-2), 95–112.

    Article  CAS  PubMed  Google Scholar 

  • Ou, L., Song, B., Liang, H., Liu, J., Feng, X., Deng, B., et al. (2016). Toxicity of graphene-family nanoparticles: A general review of the origins and mechanisms. Particle and Fibre Toxicology, 13(1), 57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pan, F., Zhang, M., Wu, G., Lai, Y., Greber, B., Scholer, H. R., et al. (2013). Topographic effect on human induced pluripotent stem cells differentiation towards neuronal lineage. Biomaterials, 34(33), 8131–8139.

    Article  CAS  PubMed  Google Scholar 

  • Pelin, M., Fusco, L., Leon, V., Martin, C., Criado, A., Sosa, S., et al. (2017). Differential cytotoxic effects of graphene and graphene oxide on skin keratinocytes. Scientific Reports, 7, 40572.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poller, B., Gutmann, H., Krahenbuhl, S., Weksler, B., Romero, I., Couraud, P. O., et al. (2008). The human brain endothelial cell line hCMEC/D3 as a human blood-brain barrier model for drug transport studies. Journal of Neurochemistry, 107(5), 1358–1368.

    Article  CAS  PubMed  Google Scholar 

  • Polli, J. E. (2008). In vitro studies are sometimes better than conventional human pharmacokinetic in vivo studies in assessing bioequivalence of immediate-release solid oral dosage forms. The AAPS Journal, 10(2), 289–299.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Potter, W., Kalil, R. E., & Kao, W. J. (2008). Biomimetic material systems for neural progenitor cell-based therapy. Frontiers in Bioscience, 13, 806–821.

    Article  CAS  PubMed  Google Scholar 

  • Prudhomme, J. G., Sherman, I. W., Land, K. M., Moses, A. V., Stenglein, S., & Nelson, J. A. (1996). Studies of plasmodium falciparum cytoadherence using immortalized human brain capillary endothelial cells. International Journal for Parasitology, 26(6), 647–655.

    Article  CAS  PubMed  Google Scholar 

  • Raghnaill, M. N., Bramini, M., Ye, D., Couraud, P. O., Romero, I. A., Weksler, B., et al. (2014). Paracrine signalling of inflammatory cytokines from an in vitro blood brain barrier model upon exposure to polymeric nanoparticles. The Analyst., 139(5), 923–930.

    Article  CAS  PubMed  Google Scholar 

  • Ragnaill, M. N., Brown, M., Ye, D., Bramini, M., Callanan, S., Lynch, I., et al. (2011). Internal benchmarking of a human blood-brain barrier cell model for screening of nanoparticle uptake and transcytosis. European Journal of Pharmaceutics and Biopharmaceutics, 77(3), 360–367.

    Article  CAS  PubMed  Google Scholar 

  • Rauti, R., Lozano, N., Leon, V., Scaini, D., Musto, M., Rago, I., et al. (2016). Graphene oxide nanosheets reshape synaptic function in cultured brain networks. ACS Nano, 10(4), 4459–4471.

    Article  CAS  PubMed  Google Scholar 

  • Regina, A., Romero, I. A., Greenwood, J., Adamson, P., Bourre, J. M., Couraud, P. O., et al. (1999). Dexamethasone regulation of P-glycoprotein activity in an immortalized rat brain endothelial cell line, GPNT. Journal of Neurochemistry, 73(5), 1954–1963.

    CAS  PubMed  Google Scholar 

  • Reichel, A., Begley, D. J., & Abbott, N. J. (2003). An overview of in vitro techniques for blood-brain barrier studies. Methods in Molecular Medicine, 89, 307–324.

    CAS  PubMed  Google Scholar 

  • Reina, G., Gonzalez-Dominguez, J. M., Criado, A., Vazquez, E., Bianco, A., & Prato, M. (2017). Promises, facts and challenges for graphene in biomedical applications. Chemical Society Reviews, 46(15), 4400–4416.

    Article  CAS  PubMed  Google Scholar 

  • Repic, T., Madirazza, K., Bektur, E., & Sapunar, D. (2016). Characterization of dorsal root ganglion neurons cultured on silicon micro-pillar substrates. Scientific Reports, 6, 39560.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roux, F., Durieu-Trautmann, O., Chaverot, N., Claire, M., Mailly, P., Bourre, J. M., et al. (1994). Regulation of gamma-glutamyl transpeptidase and alkaline phosphatase activities in immortalized rat brain microvessel endothelial cells. Journal of Cellular Physiology, 159(1), 101–113.

    Article  CAS  PubMed  Google Scholar 

  • Salinas, C. N., & Anseth, K. S. (2008). The influence of the RGD peptide motif and its contextual presentation in PEG gels on human mesenchymal stem cell viability. Journal of Tissue Engineering and Regenerative Medicine, 2(5), 296–304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salvati, A., Aberg, C., dos Santos, T., Varela, J., Pinto, P., Lynch, I., et al. (2011). Experimental and theoretical comparison of intracellular import of polymeric nanoparticles and small molecules: Toward models of uptake kinetics. Nanomedicine, 7(6), 818–826.

    Article  CAS  PubMed  Google Scholar 

  • Sandin, P., Fitzpatrick, L. W., Simpson, J. C., & Dawson, K. A. (2012). High-speed imaging of Rab family small GTPases reveals rare events in nanoparticle trafficking in living cells. ACS Nano, 6(2), 1513–1521.

    Article  CAS  PubMed  Google Scholar 

  • Sawyer, A. A., Hennessy, K. M., & Bellis, S. L. (2005). Regulation of mesenchymal stem cell attachment and spreading on hydroxyapatite by RGD peptides and adsorbed serum proteins. Biomaterials, 26(13), 1467–1475.

    Article  CAS  PubMed  Google Scholar 

  • Schnell, E., Klinkhammer, K., Balzer, S., Brook, G., Klee, D., Dalton, P., et al. (2007). Guidance of glial cell migration and axonal growth on electrospun nanofibers of poly-epsilon-caprolactone and a collagen/poly-epsilon-caprolactone blend. Biomaterials, 28(19), 3012–3025.

    Article  CAS  PubMed  Google Scholar 

  • Seabra, A. B., Paula, A. J., de Lima, R., Alves, O. L., & Duran, N. (2014). Nanotoxicity of graphene and graphene oxide. Chemical Research in Toxicology, 27(2), 159–168.

    Article  CAS  PubMed  Google Scholar 

  • Silliman, C. C., & Wang, M. (2006). The merits of in vitro versus in vivo modeling in investigation of the immune system. Environmental Toxicology and Pharmacology, 21(2), 123–134.

    Article  CAS  PubMed  Google Scholar 

  • Silva, G. A. (2005). Nanotechnology approaches for the regeneration and neuroprotection of the central nervous system. Surgical Neurology, 63(4), 301–306.

    Article  PubMed  Google Scholar 

  • Smith, Q. R., & Rapoport, S. I. (1986). Cerebrovascular permeability coefficients to sodium, potassium, and chloride. Journal of Neurochemistry, 46(6), 1732–1742.

    Article  CAS  PubMed  Google Scholar 

  • Sood, A., Salih, S., Roh, D., Lacharme-Lora, L., Parry, M., Hardiman, B., et al. (2011). Signalling of DNA damage and cytokines across cell barriers exposed to nanoparticles depends on barrier thickness. Nature Nanotechnology, 6(12), 824–833.

    Article  CAS  PubMed  Google Scholar 

  • Srikanth, M., & Kessler, J. A. (2012). Nanotechnology-novel therapeutics for CNS disorders. Nature Reviews. Neurology, 8(6), 307–318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takeshita, Y., Obermeier, B., Cotleur, A., Sano, Y., Kanda, T., & Ransohoff, R. M. (2014). An in vitro blood-brain barrier model combining shear stress and endothelial cell/astrocyte co-culture. Journal of Neuroscience Methods, 232, 165–172.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tenuta, T., Monopoli, M. P., Kim, J., Salvati, A., Dawson, K. A., Sandin, P., et al. (2011). Elution of labile fluorescent dye from nanoparticles during biological use. PLoS One, 6(10), e25556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tessier-Lavigne, M., & Goodman, C. S. (1996). The molecular biology of axon guidance. Science, 274(5290), 1123–1133.

    Article  CAS  PubMed  Google Scholar 

  • Tian, X., Yang, Z., Duan, G., Wu, A., Gu, Z., Zhang, L., et al. (2017). Graphene oxide nanosheets retard cellular migration via disruption of actin cytoskeleton. Small, 13(3). https://doi.org/10.1002/smll.201602133

  • Toomre, D., Steyer, J. A., Keller, P., Almers, W., & Simons, K. (2000). Fusion of constitutive membrane traffic with the cell surface observed by evanescent wave microscopy. The Journal of Cell Biology, 149(1), 33–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tu, Q., Pang, L., Chen, Y., Zhang, Y., Zhang, R., Lu, B., et al. (2014). Effects of surface charges of graphene oxide on neuronal outgrowth and branching. The Analyst., 139(1), 105–115.

    Article  CAS  PubMed  Google Scholar 

  • Upadhyay, R. K. (2014). Drug delivery systems, CNS protection, and the blood brain barrier. BioMed Research International, 2014, 869269.

    PubMed  PubMed Central  Google Scholar 

  • Victorio, S. C., Havton, L. A., & Oliveira, A. L. (2010). Absence of IFNgamma expression induces neuronal degeneration in the spinal cord of adult mice. Journal of Neuroinflammation, 7, 77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vu, K., Weksler, B., Romero, I., Couraud, P. O., & Gelli, A. (2009). Immortalized human brain endothelial cell line HCMEC/D3 as a model of the blood-brain barrier facilitates in vitro studies of central nervous system infection by Cryptococcus neoformans. Eukaryotic Cell, 8(11), 1803–1807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, G., Ao, Q., Gong, K., Wang, A., Zheng, L., Gong, Y., et al. (2010). The effect of topology of chitosan biomaterials on the differentiation and proliferation of neural stem cells. Acta Biomaterialia, 6(9), 3630–3639.

    Article  CAS  PubMed  Google Scholar 

  • Weerth, S. H., Holtzclaw, L. A., & Russell, J. T. (2007). Signaling proteins in raft-like microdomains are essential for Ca2+ wave propagation in glial cells. Cell Calcium, 41(2), 155–167.

    Article  CAS  PubMed  Google Scholar 

  • Weksler, B. B., Subileau, E. A., Perriere, N., Charneau, P., Holloway, K., Leveque, M., et al. (2005). Blood-brain barrier-specific properties of a human adult brain endothelial cell line. The FASEB Journal, 19(13), 1872–1874.

    Article  CAS  PubMed  Google Scholar 

  • Wick, P., Louw-Gaume, A. E., Kucki, M., Krug, H. F., Kostarelos, K., Fadeel, B., et al. (2014). Classification framework for graphene-based materials. Angewandte Chemie, 53(30), 7714–7718.

    Article  CAS  PubMed  Google Scholar 

  • Willerth, S. M. (2011). Neural tissue engineering using embryonic and induced pluripotent stem cells. Stem Cell Research and Therapy, 2(2), 17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wolff, A., Antfolk, M., Brodin, B., & Tenje, M. (2015). In vitro blood-brain barrier models—an overview of established models and new microfluidic approaches. Journal of Pharmaceutical Sciences, 104(9), 2727–2746.

    Article  CAS  PubMed  Google Scholar 

  • Yang, L., Wang, F., Han, H., Yang, L., Zhang, G., & Fan, Z. (2015). Functionalized graphene oxide as a drug carrier for loading pirfenidone in treatment of subarachnoid hemorrhage. Colloids and Surfaces. B, Biointerfaces, 129, 21–29.

    Article  CAS  PubMed  Google Scholar 

  • Ye, D., Raghnaill, M. N., Bramini, M., Mahon, E., Aberg, C., Salvati, A., et al. (2013). Nanoparticle accumulation and transcytosis in brain endothelial cell layers. Nanoscale, 5(22), 11153–11165.

    Article  CAS  PubMed  Google Scholar 

  • Zensi, A., Begley, D., Pontikis, C., Legros, C., Mihoreanu, L., Wagner, S., et al. (2009). Albumin nanoparticles targeted with Apo E enter the CNS by transcytosis and are delivered to neurones. Journal of Controlled Release, 137(1), 78–86.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, L., Ma, Z., Smith, G. M., Wen, X., Pressman, Y., Wood, P. M., et al. (2009). GDNF-enhanced axonal regeneration and myelination following spinal cord injury is mediated by primary effects on neurons. Glia, 57(11), 1178–1191.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang, X., Yin, J., Peng, C., Hu, W., Zhu, Z., Li, W., et al. (2011). Distribution and biocompatibility studies of graphene oxide in mice after intravenous administration. Carbon, 49, 986–995.

    Article  CAS  Google Scholar 

  • Zhou, H., Zhao, K., Li, W., Yang, N., Liu, Y., Chen, C., et al. (2012). The interactions between pristine graphene and macrophages and the production of cytokines/chemokines via TLR- and NF-kappaB-related signaling pathways. Biomaterials, 33(29), 6933–6942.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Mattia Bramini or Fabrizia Cesca .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Bramini, M., Rocchi, A., Benfenati, F., Cesca, F. (2019). Neuronal Cultures and Nanomaterials. In: Chiappalone, M., Pasquale, V., Frega, M. (eds) In Vitro Neuronal Networks. Advances in Neurobiology, vol 22. Springer, Cham. https://doi.org/10.1007/978-3-030-11135-9_3

Download citation

Publish with us

Policies and ethics