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Graphene Based Materials in Neural Tissue Regeneration

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Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1107)

Abstract

Due to its extraordinary features such as large surface area, high electrical conductivity, chemical stability and mechanical properties, graphene attracts great interest in various fields of biomedical sciences including biosensors, cancer therapy, diagnosis and regenerative medicine. The use of graphene-based materials has been of great interest for the design of scaffolds that can promote neural tissue regeneration. Recent studies published over the last few years clearly show that graphene and graphene based materials promote adhesion, proliferation and differentiation of various cells including embryonic stem cells (ESC), neural stem cells (NSC), mesenchymal stem cells (MSC) and induced pluripotent stem cells (iPSC). Therefore graphene based materials are one of the promising nanoplatforms in regenerative medicine for neural tissue injury. With its unique topographic and chemical properties, graphene is used as a scaffold that could provide a bridge between regenerating nerves. More importantly, as a conductive substrate, graphene allows the continuation of electrical conduction between damaged nerve ends. The integration of supportive cells such as glial, neural precursor or stem cells in such a scaffold shows higher regeneration when compared to currently used neural autografts and nerve conduits. This review discusses the details of such studies involving graphene based materials with a special interest on neural stem cells, mesenchymal stem cells or pluripotent stem cells.

Keywords

Graphene oxide Mesenchymal stem cells Neural stem cells Pluripotent stem cells 

Abbreviations

2D

Two dimentional

3D

Three dimentional

1 step-G

One-step growth

2 step-G

Two-step growth

BDNF

Brain-derived neurotrophic factor

b-FGF

Basic fibroblast growth factor

CNS

Central nervous system

Cu

Copper

ECM

Extracellular matrix

EGF

Epidermal growth factor

ELF-EMF

Extremely low frequency electromagnetic fields

ESCs

Embryonic stem cells

FGF-2

Fibroblast growth factor 2

G

Graphene

GO

Graphene oxide

hADMSCs

Human adipose-derived mesenchymal stem cells

hMSCs

Human mesenchymal stem cells

hNPCs

Human neural progenitor cells

hNSCs

Human neural stem cells

IFNγ

Interferon-γ

iPSCs

Induced pluripotent stem cells

LIF

Leukemia inhibitory factor

LPS

Lipopolysaccharide

MSCs

Mesenchymal stem cells

NGLC

Nanocrystalline glass-like carbon film

NGF

Nerve growth factor

NGO

Nanosized graphene oxide

NPCs

Neural progenitor cells

NSCs

Neural stem cells

PADM

Porcine acellular dermal matrix

PCL

Polycaprolactone

PDGF

Platelet-derived growth factor

PDMS

Polydimethylsiloxane

PEDOT

Poly (3,4-ethylenedioxythiophene)

PEG

Poly (ethylene glycol)

PN

Peripheral nerve

PNI

Peripheral nerve injury

PNS

Peripheral nervous system

PU

Polyurethane

rGO

Reduced graphene oxide

SCI

Spinal cord injury

SCs

Schwann cells

SDIA

Stromal cell-derived inducing activity

siNPs

Silica nanoparticles

TBI

Traumatic brain injury

TCPS

Tissue culture polystyrene

TiO2

Titanium dioxide

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Notes

Acknowledgement

AY, HT and CG acknowledge support by the Scientific and Technological Research Council of Turkey and FlagEra Graphene Project G-IMMUNOMICS (TUBITAK, grant number 315S202).

References

  1. Akhavan O, Ghaderi E (2013) Flash photo stimulation of human neural stem cells on graphene/TiO 2 heterojunction for differentiation into neurons. Nanoscale 5:10316–10326CrossRefPubMedGoogle Scholar
  2. Ali-Boucetta H, Bitounis D, Raveendran-Nair R, Servant A, Van den Bossche J, Kostarelos K (2013) Purified graphene oxide dispersions lack in vitro cytotoxicity and in vivo pathogenicity. Adv Healthc Mater 2:433–441CrossRefPubMedGoogle Scholar
  3. Amoh Y, Li L, Campillo R, Kawahara K, Katsuoka K, Penman S, Hoffman RM (2005) Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves. Proc Natl Acad Sci U S A 102:17734–17738CrossRefPubMedPubMedCentralGoogle Scholar
  4. Barnabé-Heider F, Frisén J (2008) Stem cells for spinal cord repair. Cell Stem Cell 3:16–24CrossRefPubMedGoogle Scholar
  5. Bitounis D, Ali-Boucetta H, Hong BH, Min DH, Kostarelos K (2013) Prospects and challenges of graphene in biomedical applications. Adv Mater 25:2258–2268CrossRefPubMedGoogle Scholar
  6. Bressan E, Ferroni L, Gardin C, Sbricoli L, Gobbato L, Ludovichetti FS, Tocco I, Carraro A, Piattelli A, Zavan B (2014) Graphene based scaffolds effects on stem cells commitment. J Transl Med 12:296CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bussy C, Ali-Boucetta H, Kostarelos K (2013) Safety considerations for graphene: lessons learnt from carbon nanotubes. Acc Chem Res 46:692–701CrossRefPubMedGoogle Scholar
  8. Chang K-A, Kim JW, a Kim J, Lee S, Kim S, Suh WH, Kim H-S, Kwon S, Kim SJ, Suh Y-H (2011) Biphasic electrical currents stimulation promotes both proliferation and differentiation of fetal neural stem cells. PLoS One 6:e18738CrossRefPubMedPubMedCentralGoogle Scholar
  9. Chen G-Y, Pang D-P, Hwang S-M, Tuan H-Y, Hu Y-C (2012) A graphene-based platform for induced pluripotent stem cells culture and differentiation. Biomaterials 33:418–427CrossRefPubMedGoogle Scholar
  10. Chen Z, Ren W, Gao L, Liu B, Pei S, Cheng H-M (2011) Three-dimensional flexible and conductive interconnected graphene networks grown by chemical vapour deposition. Nat Mater 10:424CrossRefPubMedGoogle Scholar
  11. Chin MH, Mason MJ, Xie W, Volinia S, Singer M, Peterson C, Ambartsumyan G, Aimiuwu O, Richter L, Zhang J (2009) Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell 5:111–123CrossRefPubMedPubMedCentralGoogle Scholar
  12. de Lázaro I, Yilmazer A, Kostarelos K (2014) Induced pluripotent stem (iPS) cells: a new source for cell-based therapeutics? J Control Release 185:37–44CrossRefPubMedGoogle Scholar
  13. del Río-Hortega P (1921) Estudios sobre la neurogia. La glia de escasas rediaciones (oligodendroglia). Bol Real Soc Esp Hist Nat 21:63–92Google Scholar
  14. del Río-Hortega P (1928) Tercera aportación al conocimiento morfológico e interpretación funcional de la oligodendroglıá. Mem Real Soc Esp Hist Nat 14:5–122Google Scholar
  15. Ding X, Liu H, Fan Y (2015) Graphene-based materials in regenerative medicine. Adv Healthc Mater 4:1451–1468CrossRefPubMedGoogle Scholar
  16. Fraczek-Szczypta A (2014) Carbon nanomaterials for nerve tissue stimulation and regeneration. Mater Sci Eng C 34:35–49CrossRefGoogle Scholar
  17. Frostick SP, Yin Q, Kemp GJ (1998) Schwann cells, neurotrophic factors, and peripheral nerve regeneration. Microsurgery 18:397–405CrossRefPubMedGoogle Scholar
  18. Gardin C, Piattelli A, Zavan B (2016) Graphene in regenerative medicine: focus on stem cells and neuronal differentiation. Trends Biotechnol 34:435–437CrossRefPubMedGoogle Scholar
  19. Geim AK (2011) Nobel lecture: random walk to graphene. Rev Mod Phys 83:851CrossRefGoogle Scholar
  20. Ghasemi-Mobarakeh L, Prabhakaran MP, Morshed M, Nasr-Esfahani MH, Baharvand H, Kiani S, Al-Deyab SS, Ramakrishna S (2011) Application of conductive polymers, scaffolds and electrical stimulation for nerve tissue engineering. J Tissue Eng Regen Med 5:e17CrossRefPubMedGoogle Scholar
  21. Gomillion CT, Burg KJ (2006) Stem cells and adipose tissue engineering. Biomaterials 27:6052–6063CrossRefPubMedGoogle Scholar
  22. Guo W, Qiu J, Liu J, Liu H (2017) Graphene microfiber as a scaffold for regulation of neural stem cells differentiation. Sci Rep 7:5678CrossRefPubMedPubMedCentralGoogle Scholar
  23. Guo W, Wang S, Yu X, Qiu J, Li J, Tang W, Li Z, Mou X, Liu H, Wang Z (2016a) Construction of a 3D rGO–collagen hybrid scaffold for enhancement of the neural differentiation of mesenchymal stem cells. Nanoscale 8:1897–1904CrossRefPubMedGoogle Scholar
  24. Guo W, Zhang X, Yu X, Wang S, Qiu J, Tang W, Li L, Liu H, Wang ZL (2016b) Self-powered electrical stimulation for enhancing neural differentiation of mesenchymal stem cells on graphene–poly (3, 4-ethylenedioxythiophene) hybrid microfibers. ACS Nano 10:5086–5095CrossRefPubMedGoogle Scholar
  25. Huang C-T, Shrestha LK, Ariga K, Hsu S-h (2017) A graphene–polyurethane composite hydrogel as a potential bioink for 3D bioprinting and differentiation of neural stem cells. J Mater Chem B 5:8854–8864CrossRefGoogle Scholar
  26. Jakus AE, Secor EB, Rutz AL, Jordan SW, Hersam MC, Shah RN (2015) Three-dimensional printing of high-content graphene scaffolds for electronic and biomedical applications. ACS Nano 9:4636–4648CrossRefPubMedGoogle Scholar
  27. Kenry LWC, Loh KP, Lim CT (2018) When stem cells meet graphene: opportunities and challenges in regenerative medicine. Biomaterials 155:236–250.  https://doi.org/10.1016/j.biomaterials.2017.10.004 CrossRefPubMedGoogle Scholar
  28. Kim J, Park S, Kim YJ, Jeon CS, Lim KT, Seonwoo H, Cho S-P, Chung TD, Choung P-H, Choung Y-H (2015a) Monolayer graphene-directed growth and neuronal differentiation of mesenchymal stem cells. J Biomed Nanotechnol 11:2024–2033CrossRefPubMedGoogle Scholar
  29. Kim T-H, Shah S, Yang L, Yin PT, Hossain MK, Conley B, Choi J-W, Lee K-B (2015b) Controlling differentiation of adipose-derived stem cells using combinatorial graphene hybrid-pattern arrays. ACS Nano 9:3780–3790CrossRefPubMedPubMedCentralGoogle Scholar
  30. Lee-Kubli CA, Lu P (2015) Induced pluripotent stem cell-derived neural stem cell therapies for spinal cord injury. Neural Regen Res 10:10CrossRefPubMedPubMedCentralGoogle Scholar
  31. Lee WC, Lim CHY, Shi H, Tang LA, Wang Y, Lim CT, Loh KP (2011) Origin of enhanced stem cell growth and differentiation on graphene and graphene oxide. ACS Nano 5:7334–7341CrossRefPubMedPubMedCentralGoogle Scholar
  32. Lee Y-J, Jang W, Im H, Sung J-S (2015) Extremely low frequency electromagnetic fields enhance neuronal differentiation of human mesenchymal stem cells on graphene-based substrates. Curr Appl Phys 15:S95–S102CrossRefGoogle Scholar
  33. Lee YJ, Seo TH, Lee S, Jang W, Kim MJ, Sung JS (2018) Neuronal differentiation of human mesenchymal stem cells in response to the domain size of graphene substrates. J Biomed Mater Res A 106:43–51CrossRefGoogle Scholar
  34. Li N, Zhang Q, Gao S, Song Q, Huang R, Wang L, Liu L, Dai J, Tang M, Cheng G (2013) Three-dimensional graphene foam as a biocompatible and conductive scaffold for neural stem cells. Sci Rep 3:1604CrossRefPubMedPubMedCentralGoogle Scholar
  35. Liu S, Qu Y, Stewart TJ, Howard MJ, Chakrabortty S, Holekamp TF, McDonald JW (2000) Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation. Proc Natl Acad Sci 97:6126–6131CrossRefGoogle Scholar
  36. López-Dolado E, González-Mayorga A, Portolés MT, Feito MJ, Ferrer ML, del Monte F, Gutiérrez MC, Serrano MC (2015) Subacute tissue response to 3D graphene oxide scaffolds implanted in the injured rat spinal cord. Adv Healthc Mater 4:1861–1868CrossRefGoogle Scholar
  37. Nayak TR, Andersen H, Makam VS, Khaw C, Bae S, Xu X, Ee P-LR, Ahn J-H, Hong BH, Pastorin G (2011) Graphene for controlled and accelerated osteogenic differentiation of human mesenchymal stem cells. ACS Nano 5:4670–4678CrossRefPubMedPubMedCentralGoogle Scholar
  38. Nedergaard M (1994) Direct signaling from astrocytes to neurons in cultures of mammalian brain cells. Science 263:1768–1771CrossRefPubMedPubMedCentralGoogle Scholar
  39. Nguyen AT, Mattiassi S, Loeblein M, Chin E, Ma D, Coquet P, Viasnoff V, Teo EHT, Goh EL, Yim EK (2018) Human Rett-derived neuronal progenitor cells in 3D graphene scaffold as an in vitro platform to study the effect of electrical stimulation on neuronal differentiation. Biomed Mater 13:034111CrossRefPubMedPubMedCentralGoogle Scholar
  40. Novoselov KS (2011) Graphene: materials in the flatland (Nobel Lecture). Angew Chem Int Ed 50:6986–7002CrossRefGoogle Scholar
  41. Novoselov KS, Geim AK, Morozov SV, Jiang D, Zhang Y, Dubonos SV, Grigorieva IV, Firsov AA (2004) Electric field effect in atomically thin carbon films. Science 306:666–669CrossRefPubMedGoogle Scholar
  42. Okan BS, Marset A, Seyyed Monfared Zanjani J, Sut PA, Sen O, Çulha M, Menceloglu Y (2016) Thermally exfoliated graphene oxide reinforced fluorinated pentablock poly (l-lactide-co-ε-caprolactone) electrospun scaffolds: insight into antimicrobial activity and biodegradation. J Appl Polym Sci 133(22):43490Google Scholar
  43. Park J, Park S, Ryu S, Bhang SH, Kim J, Yoon JK, Park YH, Cho SP, Lee S, Hong BH (2014) Graphene–regulated Cardiomyogenic differentiation process of mesenchymal stem cells by enhancing the expression of extracellular matrix proteins and cell signaling molecules. Adv Healthc Mater 3:176–181CrossRefPubMedGoogle Scholar
  44. Park SY, Park J, Sim SH, Sung MG, Kim KS, Hong BH, Hong S (2011) Enhanced differentiation of human neural stem cells into neurons on graphene. Adv Mater 23:H263CrossRefPubMedGoogle Scholar
  45. Ramírez-Jarquín UN, Lazo-Gomez R, Tovar-y-Romo LB, Tapia R (2014) Spinal inhibitory circuits and their role in motor neuron degeneration. Neuropharmacology 82:101–107CrossRefPubMedGoogle Scholar
  46. Reina G, Tamburri E, Orlanducci S, Gay S, Matassa R, Guglielmotti V, Lavecchia T, Letizia Terranova M, Rossi M (2014) Nanocarbon surfaces for biomedicine. Biomatter 4:e28537CrossRefPubMedPubMedCentralGoogle Scholar
  47. Rodriguez-Losada N, Romero P, Estivill-Torrús G, de Villoria RG, Aguirre JA (2017) Cell survival and differentiation with nanocrystalline glass-like carbon using substantia nigra dopaminergic cells derived from transgenic mouse embryos. PLoS One 12:e0173978CrossRefPubMedPubMedCentralGoogle Scholar
  48. Salewski RP, Eftekharpour E, Fehlings MG (2010) Are induced pluripotent stem cells the future of cell-based regenerative therapies for spinal cord injury. J Cell Physiol 222:515–521PubMedGoogle Scholar
  49. Saner B, Okyay F, Yürüm Y (2010) Utilization of multiple graphene layers in fuel cells. 1. An improved technique for the exfoliation of graphene-based nanosheets from graphite. Fuel 89:1903–1910CrossRefGoogle Scholar
  50. Scholz J, Woolf CJ (2007) The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 10:1361CrossRefPubMedGoogle Scholar
  51. Schroeder GD, Kepler CK, Vaccaro AR (2016) The use of cell transplantation in spinal cord injuries. J Am Acad Orthop Surg 24:266–275CrossRefPubMedGoogle Scholar
  52. Seabra AB, Paula AJ, de Lima R, Alves OL, Duran N (2014) Nanotoxicity of graphene and graphene oxide. Chem Res Toxicol 27:159–168CrossRefPubMedGoogle Scholar
  53. Sedaghati T, Yang SY, Mosahebi A, Alavijeh MS, Seifalian AM (2011) Nerve regeneration with aid of nanotechnology and cellular engineering. Biotechnol Appl Biochem 58:288–300CrossRefPubMedGoogle Scholar
  54. Serrano M, Patiño J, García-Rama C, Ferrer M, Fierro J, Tamayo A, Collazos-Castro J, Del Monte F, Gutierrez M (2014) 3D free-standing porous scaffolds made of graphene oxide as substrates for neural cell growth. J Mater Chem B 2:5698–5706CrossRefGoogle Scholar
  55. Shah S, Solanki A, Lee KB (2016) Nanotechnology-based approaches for guiding neural regeneration. Acc Chem Res 49:17–26.  https://doi.org/10.1021/acs.accounts.5b00345 CrossRefPubMedGoogle Scholar
  56. Shah S, Yin PT, Uehara TM, Chueng STD, Yang L, Lee KB (2014) Guiding stem cell differentiation into oligodendrocytes using graphene-nanofiber hybrid scaffolds. Adv Mater 26:3673–3680CrossRefPubMedPubMedCentralGoogle Scholar
  57. Shin SR, Li YC, Jang HL, Khoshakhlagh P, Akbari M, Nasajpour A, Zhang YS, Tamayol A, Khademhosseini A (2016) Graphene-based materials for tissue engineering. Adv Drug Deliv Rev 105:255–274.  https://doi.org/10.1016/j.addr.2016.03.007 CrossRefPubMedPubMedCentralGoogle Scholar
  58. Silva GA (2006) Neuroscience nanotechnology: progress, opportunities and challenges. Nat Rev Neurosci 7:65CrossRefPubMedGoogle Scholar
  59. Slonczewski J, Weiss P (1958) Band structure of graphite. Phys Rev 109:272CrossRefGoogle Scholar
  60. Solanki A, Chueng STD, Yin PT, Kappera R, Chhowalla M, Lee KB (2013) Axonal alignment and enhanced neuronal differentiation of neural stem cells on graphene-nanoparticle hybrid structures. Adv Mater 25:5477–5482CrossRefPubMedPubMedCentralGoogle Scholar
  61. Song Q, Jiang Z, Li N, Liu P, Liu L, Tang M, Cheng G (2014) Anti-inflammatory effects of three-dimensional graphene foams cultured with microglial cells. Biomaterials 35:6930–6940CrossRefPubMedGoogle Scholar
  62. Spassky N, Merkle FT, Flames N, Tramontin AD, García-Verdugo JM, Alvarez-Buylla A (2005) Adult ependymal cells are postmitotic and are derived from radial glial cells during embryogenesis. J Neurosci 25:10–18CrossRefPubMedGoogle Scholar
  63. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676CrossRefPubMedGoogle Scholar
  64. Terenghi G (1999) Peripheral nerve regeneration and neurotrophic factors. J Anat 194:1–14CrossRefPubMedPubMedCentralGoogle Scholar
  65. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147CrossRefPubMedGoogle Scholar
  66. Ullah I, Subbarao RB, Rho GJ (2015) Human mesenchymal stem cells-current trends and future prospective. Biosci Rep 35:e00191CrossRefPubMedPubMedCentralGoogle Scholar
  67. Venables J, Spiller G, Hanbucken M (1984) Nucleation and growth of thin films. Rep Prog Phys 47:399CrossRefGoogle Scholar
  68. Wang Y, Lee WC, Manga KK, Ang PK, Lu J, Liu YP, Lim CT, Loh KP (2012) Fluorinated graphene for promoting neuro-induction of stem cells. Adv Mater 24:4285–4290CrossRefPubMedGoogle Scholar
  69. Weaver CL, Cui XT (2015) Directed neural stem cell differentiation with a functionalized graphene oxide nanocomposite. Adv Healthc Mater 4:1408–1416CrossRefPubMedGoogle Scholar
  70. Wyndaele M, Wyndaele J-J (2006) Incidence, prevalence and epidemiology of spinal cord injury: what learns a worldwide literature survey? Spinal Cord 44:523CrossRefPubMedGoogle Scholar
  71. Yang D, Li T, Xu M, Gao F, Yang J, Yang Z, Le W (2014) Graphene oxide promotes the differentiation of mouse embryonic stem cells to dopamine neurons. Nanomedicine 9:2445–2455CrossRefPubMedGoogle Scholar
  72. Barkho BZ, Zhao X (2011) Adult neural stem cells: response to stroke injury and potential for therapeutic applications. Curr Stem Cell Res Ther 6:327–338CrossRefPubMedPubMedCentralGoogle Scholar
  73. Zhou K, Nisbet D, Thouas G, Bernard C, Forsythe J (2010) Bio-nanotechnology approaches to neural tissue engineering. In: Tissue engineering. InTech, RijekaGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Biotechnology InstituteAnkara UniversityTandogan/AnkaraTurkey
  2. 2.Engineering Faculty, Biomedical Engineering DepartmentAnkara UniversityTandogan/AnkaraTurkey
  3. 3.Stem Cell InstituteAnkara UniversityBalgat/AnkaraTurkey

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