Interfacing Graphene-Based Materials With Neural Cells

Abstract

The scientific community has witnessed an exponential increase in the applications of graphene and graphene-based materials in a wide range of fields, from engineering to electronics to biotechnologies and biomedical applications. For what concerns neuroscience, the interest raised by these materials is two-fold. On one side, nanosheets made of graphene or graphene derivatives (graphene oxide, or its reduced form) can be used as carriers for drug delivery. Here, an important aspect is to evaluate their toxicity, which strongly depends on flake composition, chemical functionalization and dimensions. On the other side, graphene can be exploited as a substrate for tissue engineering. In this case, conductivity is probably the most relevant amongst the various properties of the different graphene materials, as it may allow to instruct and interrogate neural networks, as well as to drive neural growth and differentiation, which holds a great potential in regenerative medicine. In this review, we try to give a comprehensive view of the accomplishments and new challenges of the field, as well as which in our view are the most exciting directions to take in the immediate future. These include the need to engineer multifunctional nanoparticles (NPs) able to cross the blood-brain-barrier to reach neural cells, and to achieve on-demand delivery of specific drugs. We describe the state-of-the-art in the use of graphene materials to engineer three-dimensional scaffolds to drive neuronal growth and regeneration in vivo, and the possibility of using graphene as a component of hybrid composites/multi-layer organic electronics devices. Last but not least, we address the need of an accurate theoretical modeling of the interface between graphene and biological material, by modeling the interaction of graphene with proteins and cell membranes at the nanoscale, and describing the physical mechanism(s) of charge transfer by which the various graphene materials can influence the excitability and physiology of neural cells.

Viability of Neural Cells on 3D Printed Graphene Bioelectronics

“…From the live-dead cell assay results, it appeared that N27 cells successfully grew on the graphene and Kapton substrate, confirming our earlier hypothesis [69,70]. It has been discussed in tissue-engineering literature that graphene may negatively affect the bimolecular mechanisms responsible for biological safety and toxicity [71][72][73][74]. Many reports have claimed that oxidative stress is one mechanism of cytotoxicity originating from carbon-based nanomaterials [75].…”

Monolayer Graphene Coating of Intracortical Probes for Long‐Lasting Neural Activity Monitoring

“…In our study, we have previously shown that CVD‐grown graphene combines both positive and stretched surface which are indeed two crucial features sustaining neural outgrowth, and that poor crystalline quality could significantly impede the neural adhesion and growth. Graphene also offers a flexibility at the cell scale compared to rigid substrate which could also play a significant role in the neurite sprouting and cell motility, in addition to other biosuitable properties of graphene, such as nanoscale structure, robust, mechanically deformable, electrical conductivity, and absorption of biomolecules . This unique combination gathered in a single material can indeed collectively support the neurons regrowth and improve the acceptance of the foreign interface.…”

Graphene Promotes Axon Elongation through Local Stall of Nerve Growth Factor Signaling Endosomes

“…In the last case, an interesting increased neurite sprouting and outgrowth induced by graphene were reported for hippocampal neurons 1 , differentiated SH-SY5Y neuroblastoma cell line 5 , adrenal phaeochromocytoma (PC12) cell line 4,6,7 , dorsal root ganglion (DRG) neurons 4 and neural stem cells 8 . Such feature makes graphene appealing for application in peripheral nerve regeneration, where an appropriate scaffold may accelerate neurite outgrowth 9,10 . However, to date, few studies have examined the interaction of graphene with peripheral neurons.…”