Carbon-based smart nanomaterials in biomedicine and neuroengineering

Abstract

The search for advanced biomimetic materials that are capable of offering a scaffold for biological tissues during regeneration or of electrically connecting artificial devices with cellular structures to restore damaged brain functions is at the forefront of interdisciplinary research in materials science. Bioactive nanoparticles for drug delivery, substrates for nerve regeneration and active guidance, as well as supramolecular architectures mimicking the extracellular environment to reduce inflammatory responses in brain implants, are within reach thanks to the advancements in nanotechnology. In particular, carbon-based nanostructured materials, such as graphene, carbon nanotubes (CNTs) and nanodiamonds (NDs), have demonstrated to be highly promising materials for designing and fabricating nanoelectrodes and substrates for cell growth, by virtue of their peerless optical, electrical, thermal, and mechanical properties. In this review we discuss the state-of-the-art in the applications of nanomaterials in biological and biomedical fields, with a particular emphasis on neuroengineering.

Keywords: carbon nanotubes; electrophysiology; graphene; microelectrodes; nanodiamonds; nanotechnology; neuroengineering; neuronal cultures; neuroscience.

Figure 1

Flexible MEA developed by Lin and colleagues. SEM micrographs showing vertically aligned CNTs on Parylene-C (a,b) and a photo of the transparent flexible CNTs electrodes (c). Reproduced and modified from [116] with permission. Copyright 2009 Elsevier.

Figure 2

CNTs thin-films are optimal substrates for neuronal growth and development ex vivo (A–C) and improve spontaneous synaptic activity, as shown by the increased frequency of (D) post-synaptic currents and of (E) action potentials. Reproduced and modified from [118] with permission. Copyright 2005 American Chemical Society.

Figure 3

CNTs affect single-neuron excitability, inducing depolarising after-potentials (a). This behaviour is specifically attributable to CNTs, as it has been observed neither for cells grown on smooth and electrically conducting indium tin oxide substrates (ito) nor on electrically-insulating RADA16 peptide thin-films (b), characterised by a similar nanoscale roughness s CNTs (c). The culture substrates do not alter the electrical passive properties of neuronal membranes (d). Reproduced and modified from [121] with permission. Copyright 2009 Nature Publishing Group.

Figure 4

Scanning electron micrographs show that, when exposed to animal blood serum proteins, polycrystalline (PCD) and nanocrystalline diamond (NCD) substrates performed as good as glass or silicon substrates (a). NDs coating did not alter single-cell excitability (b). Reproduced and modified from [130] with permission. Copyright 2010 Elsevier.

Figure 5

Sketch of the device for recording the extracellular electrical activity of cultured neuronal networks, developed by Ariano and co-workers. Cells (4) are plated in the recording chamber (8), directly onto hydrogen-terminated diamond (5). Reproduced from [128] with permission. Copyright 2009 Elsevier.

Figure 6

Three-dimensional graphene foam scaffolds allow neural stem cells to adhere and improve their proliferation by up-regulating Ki-67 protein expression. Reproduced from [146] with permission. Copyright 2013 Nature Publishing Group.