Interfacing graphene with peripheral neurons: influence of neurite outgrowth and NGF axonal transport

Graphene displays properties that make it appealing for neuroregenerative medicine, yet the potential of large-scale highly-crystalline graphene as a conductive peripheral neural interface has been scarcely investigated. In particular, pristine graphene offers enhanced electrical properties that can be advantageous for nervous system regeneration applications. In this work, we investigate graphene potential as peripheral nerve interface. First, we perform an unprecedented analysis aimed at revealing how the typical polymeric coatings for neural cultures distribute on graphene at the nanometric scale. Second, we examine the impact of graphene on the culture of two established cellular models for peripheral nervous system: PC12 cell line and primary embryonic rat dorsal root ganglion (DRG) neurons, showing a better and faster axonal elongation using graphene. We then observe that the axon elongation in the first days of culture correlates to an altered nerve growth factor (NGF) axonal transport, with a reduced number of retrogradely moving NGF vesicles in favor of stalled vesicles. We thus hypothesize that the axon elongation observed in the first days of culture could be mediated by this pool of NGF vesicles locally retained in the medial/distal parts of axons. Furthermore, we investigate electrophysiological properties and cytoskeletal structure of peripheral neurons. We observe a reduced neural excitability and altered membrane potential together with a reduced inter-microtubular distance on graphene and correlate these electrophysiological and structural reorganizations of axon physiology to the observed vesicle stalling. Finally, the potential of another 2D material as neural interface, tungsten disulfide, is explored

erratum to superlubricity of epitaxial monolayer ws2 on graphene

The article Superlubricity of epitaxial monolayer WS2 on graphene, written by Holger Buch, Antonio Rossi, Stiven Forti, Domenica Convertino, Valentina Tozzini, and Camilla Coletti, was originally published electronically on the publisher's internet portal (currently SpringerLink) on June 18th 2018 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed in August 2018 to © The Author(s) 2018 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made. The original article has been corrected

Graphene-based nanomaterials for peripheral nerve regeneration

Emerging nanotechnologies offer numerous opportunities in the field of regenerative medicine and have been widely explored to design novel scaffolds for the regeneration and stimulation of nerve tissue. In this review, we focus on peripheral nerve regeneration. First, we introduce the biomedical problem and the present status of nerve conduits that can be used to guide, fasten and enhance regeneration. Then, we thoroughly discuss graphene as an emerging candidate in nerve tissue engineering, in light of its chemical, tribological and electrical properties. We introduce the graphene forms commonly used as neural interfaces, briefly review their applications, and discuss their potential toxicity. We then focus on the adoption of graphene in peripheral nervous system applications, a research field that has gained in the last years ever-increasing attention. We discuss the potential integration of graphene in guidance conduits, and critically review graphene interaction not only with peripheral neurons, but also with non-neural cells involved in nerve regeneration; indeed, the latter have recently emerged as central players in modulating the immune and inflammatory response and accelerating the growth of new tissue

Rapid CVD growth of millimetre-sized single crystal graphene using a cold-wall reactor

In this work we present a simple pathway to obtain large single-crystal graphene on copper (Cu) foils with high growth rates using a commercially available cold-wall chemical vapour deposition (CVD) reactor. We show that graphene nucleation density is drastically reduced and crystal growth is accelerated when: i) using ex-situ oxidised foils; ii) performing annealing in an inert atmosphere prior to growth; iii) enclosing the foils to lower the precursor impingement flux during growth. Growth rates as high as 14.7 and 17.5 micrometers per minute are obtained on flat and folded foils, respectively. Thus, single-crystal grains with lateral size of about one millimetre can be obtained in just one hour. The samples are characterised by optical microscopy, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy as well as selected area electron diffraction (SAED) and low-energy electron diffraction (LEED), which confirm the high quality and homogeneity of the films. The development of a process for the quick production of large grain graphene in a commonly used commercial CVD reactor is a significant step towards an increased accessibility to millimetre-sized graphene crystals.Comment: Article: 7 pages, 6 figures. Supplementary Information: 5 pages, 7 figure

Scalable High-Mobility Graphene/hBN Heterostructures

Graphene-hexagonal boron nitride (hBN) scalable heterostructures are pivotal for the development of graphene-based high-tech applications. In this work, we demonstrate the realization of high-quality graphene-hBN heterostructures entirely obtained with scalable approaches. hBN continuous films were grown via ion beam-assisted physical vapor deposition directly on commercially available $SiO_2/Si$ and used as receiving substrates for graphene single-crystal matrixes grown by chemical vapor deposition on copper. The structural, chemical, and electronic properties of the heterostructure were investigated by atomic force microscopy, Raman spectroscopy, and electrical transport measurements. We demonstrate graphene carrier mobilities exceeding $10,000 cm^2/Vs$ in ambient conditions, 30% higher than those directly measured on $SiO_{2}/Si$. We prove the scalability of our approach by measuring more than 100 transfer length method devices over a centimeter scale, which present an average carrier mobility of $7500 \pm 850 cm^{2}/Vs$. The reported high-quality all-scalable heterostructures are of relevance for the development of graphene-based high-performing electronic and optoelectronic applications

Human TrkAR649W mutation impairs nociception, sweating and cognitive abilities: a mouse model of HSAN IV

A functional nerve growth factor (NGF)-TrkA system is an essential requisite for the generation and maintenance of long-lasting thermal and mechanical hyperalgesia in adult mammals. Indeed, mutations in the gene encoding for TrkA are responsible for a rare condition, named Hereditary Sensory and Autonomic Neuropathy type IV (HSAN IV), characterized by the loss of response to noxious stimuli, anhidrosis and cognitive impairment. However, to date, there is no available mouse model to properly understand how the NGF-TrkA system can lead to pathological phenotypes that are distinctive of HSAN IV. Here, we report the generation of a knock-in mouse line carrying the HSAN IV TrkAR649W mutation. First, by in vitro biochemical and biophysical analyses, we show that the pathological R649W mutation leads to kinase-inactive TrkA also affecting its membrane dynamics and trafficking. In agreement with the HSAN IV human phenotype, TrkAR649W/m mice display a lower response to thermal and chemical noxious stimuli, correlating with reduced skin innervation, in addition to decreased sweating in comparison to TrkAh/m controls. Moreover, the R649W mutation decreases anxiety-like behavior and compromises cognitive abilities, by impairing spatial-working and social memory. Our results further uncover unexplored roles of TrkA in thermoregulation and sociability. In addition to accurately recapitulating the clinical manifestations of HSAN IV patients, our findings contribute to clarify the involvement of the NGF-TrkA system in pain sensation

Optical Response of CVD-Grown ML-WS2 Flakes on an Ultra-Dense Au NP Plasmonic Array

The combination of metallic nanostructures with two-dimensional transition metal dichalcogenides is an efficient way to make the optical properties of the latter more appealing for opto-electronic applications. In this work, we investigate the optical properties of monolayer WS2 flakes grown by chemical vapour deposition and transferred onto a densely-packed array of plasmonic Au nanoparticles (NPs). The optical response was measured as a function of the thickness of a dielectric spacer intercalated between the two materials and of the system temperature, in the 75–350 K range. We show that a weak interaction is established between WS2 and Au NPs, leading to temperature- and spacer-thickness-dependent coupling between the localized surface plasmon resonance of Au NPs and the WS2 exciton. We suggest that the closely-packed morphology of the plasmonic array promotes a high confinement of the electromagnetic field in regions inaccessible by the WS2 deposited on top. This allows the achievement of direct contact between WS2 and Au while preserving a strong connotation of the properties of the two materials also in the hybrid system