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OBJECTIVE: Graphene and derived materials are a new class of fundamental nanomaterials. Thanks to the unique characteristics as excellent electrical conductivity, biocompatibility and thermal properties, this material has aroused a considerable interest in the scientific community from its discovery. The purpose of this work is to pursue the various steps chronologically that led from discovery to single production and in series of graphene, focusing on the advantages and disadvantages of the techniques going to underline the validity and importance of each, on the basis of the searches to be carried out and the products finished to be obtained. In the second section of this work, however, we focused on the evolution of the applications of this super material over time. In fact, graphene and bidimensional materials in graphene have been significantly used in various areas of biomedical research such as fabric engineering, regenerative medicine, bioimaging with application in neural engineering and in the clinic, with different future perspectives still to be completed.
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Annali di stomatologia
Quantum points of graphene
Graphene: excursus of the evolution of processes and products
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G. Palumbo
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Department of Mechanics Management and Mathematics (DMMM), Politecnico di Bari, Italy
1971-1441
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Quantum points of graphene
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Graphene: excursus of the evolution of processes and products
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                                                                                                              Article


Graphene: excursus of the evolution
of processes and products


M. Covelli1                                                material with a thickness of a single atom: the graphene.
A. Cusanno2                                                Scientists successfully separated graphene from graph-
E. Aiello3                                                 ite through micromechanical stripping and this discovery
A. Greco Lucchina4                                         led them to win the Nobel Prize for Physics 2010 togeth-
A. Mastroianni 5                                           er. The graphene, a basic constitutive element of graphic
F.M. Ceruso5                                               materials, is a two -dimensional material consisting of 6
G. Palumbo2°                                               tied sp2 carbon atoms that are strictly packed in a bee
                                                           honeycomb network with an entire distance of 1.42 Å1.
1
  CIRPAS, University of Bari, Italy                        Among all sp2 to carbon allotropes, the graphene shows
2
  Department of Mechanics Management and Math-             the most remarkable and interesting chemical and phys-
  ematics (DMMM), Politecnico di Bari, Italy               ical properties such as an ultraelected electronic mobility
3
  Marrelli Health, Tecnologica Research Institute, Italy   (~ 2 × 10.5 cm2/vs), high thermal conductivity with an
4
  Saint Camillus International University of Health and    exceptional value of 3,500–5,000 W/MK (superior to any
  Medical Science, Rome, Italy.                            other material) and an electric conductivity with a critical
5
  Department of Dentistry “Fra G.B. Orsenigo” – Osped-     current density of 108 A/cm2. In summary, it can there-
  ale San Pietro F.B.F., Rome, Italy                       fore be said that this material has high chemical and me-
° Co-Last Authors                                          chanical resistance, an excellent thermal and electrical
                                                           transport and a high transparency2.
*Corresponding author:
Elisabetta Aiello; e-mail: research@tecnologicasrl.com
                                                           Process Evolution: Production Techniques
                                                           Graphene was isolated for the first time in 2004 using
Abstract                                                   a very simple and inexpensive technique, namely, the
                                                           mechanical exfoliation of graphite by means of a scotch
OBJECTIVE: Graphene and derived materials are a            tape. Since that time, other production techniques have
new class of fundamental nanomaterials. Thanks to          been studied and tested, each aimed at producing sam-
the unique characteristics as excellent electrical con-    ples suitable for different applications and uses. Cur-
ductivity, biocompatibility and thermal properties,        rently, various methods for producing graphene have
this material has aroused a considerable interest          been developed, with different approaches based on
in the scientific community from its discovery. The        size, shape of the flakes, quality and quantity. Although,
purpose of this work is to pursue the various steps        in addition to their possible applications, the techniques
chronologically that led from discovery to single pro-     are limited to: mechanical exfoliation, liquid phase ex-
duction and in series of graphene, focusing on the         foliation suitable for mass production, chemical vapour
advantages and disadvantages of the techniques go-         deposition (CVD), chemical reduction of graphene ox-
ing to underline the validity and importance of each,      ide. One of the main challenges currently appears to
on the basis of the searches to be carried out and the     be the mass production of high quality graphene with
products finished to be obtained. In the second sec-       few or no contaminants and / or defects and large par-
tion of this work, however, we focused on the evolu-       ticle size at an almost low cost. Commonly, the meth-
tion of the applications of this super material over       ods used for the synthesis of graphene from different
time. In fact, graphene and bidimensional materials        sources can be divided into top-down (exfoliation and
in graphene have been significantly used in various        reduction) and bottom-up (chemical vapour deposition)
areas of biomedical research such as fabric engi-          approaches.
neering, regenerative medicine, bioimaging with ap-
plication in neural engineering and in the clinic, with
different future perspectives still to be completed.       Mechanical Exfoliation

Key words: Graphene, Graphene oxide, Bioimag-              The first preparation method used, whose first attempts
ing, Regenerative medicine, Quantum points of gra-         were made in 1998, is mechanical exfoliation. It is the
phene.                                                     simplest method that made it possible for the first time
                                                           to synthesize graphene. In this technique, a piece of
                                                           graphite was subjected to repeated exfoliation and then
Introduction
                                                           transferred to a substrate; specifically, there is the appli-
In 2004 two physicists A. Gem and K. Novoselov of the      cation of a force to the surface of highly oriented graphite
University of Manchester areolated for the first time a    crystals to detach and divide the crystalline layers to ob-


Annali di Stomatologia 2020; XIII (1-4): 15-20                                                                             15
     Graphene: excursus of the evolution of processes and products

     tain a single one. Initially, the interaction of AFM (atom-       suspension is then subjected to mixing through ultra-
     ic force microscope) and STM (tunnelling microscope)              sonic waves, or high shear mixer. These processes
     analysis tips with the graphite surface was exploited to          create both shear and cavitation forces inside the liq-
     provide sufficient energy to overcome inter-plane attrac-         uid that cause the graphite crystals to break, reducing
     tion forces and lead to removal and isolation. of the crys-       them to ever thinner sheets, therefore, single sheets of
     talline monoatomic layer. Later, a much simpler method            graphene. The suspension resulting from the process is
     was developed, called the scotch-tape method, which               then purified by ultracentrifugation. Higher spin speeds
     used simple masking tape to exfoliate graphite. The               result in thinner flakes but with a small lateral dimen-
     technique consisted of placing the surface of a graph-            sion, which reduce utility for applications such as com-
     ite crystal on the adhesive tape, peeling off the tape            posites. The number of graphene layers (N), i.e. the
     and thus peeling a few layers of material. The tape with          thickness of the exfoliated graphite material, is usually
     the graphite imprint was then folded back on itself and           determined by transmission electron microscopy (TEM)
     this action was carried out several times. At the end of          and atomic force microscopy (AFM). This method is
     the process, the thin adhered flakes were easily trans-           more promising from the point of view of scalability and
     ferred to an insulating substrate. Mechanical exfoliation         allows to obtain large quantities of excellent material.
     is the simplest and most accessible method of isolating           In contrast, graphene flakes turn out to be small as side
     graphene flakes of the size of a few square microns,              dimensions. In addition, the use of reactive solvents
     useful for basic research and laboratory scale experi-            could increase costs and the process itself is not very
     ments producing very high quality crystals, but unfortu-          ecological due to the heavy use of solvents, given the
     nately, it is not suitable for a production industrial as it is   low solubility of graphene6.
     not possible to increase the process3.
                                                                       Chemical Vapour Deposition (CVD)
     Chemical Reduction of Graphene Oxide (GO).
                                                                       Subsequently, in 2008-2009, the chemical vapour depo-
     Until now, all studies had focused on the exfoliation of          sition (CVD) method was reported, which is one of the
     graphite oxide and subsequent reduction to graphene.              most useful methods for preparing high quality structur-
     From after 2006, however, graphene was synthesized                al monolayer graphene to be used for different devices.
     by reduction of graphene oxide. Various chemical and              To date, several types of CVD methods are available
     thermal reduction methods have been tested which                  such as plasma enhanced CVD, thermal CVD, hot /
     have produced materials with conductivity in the order            cold wall CVD and many others. Large samples can
     of 102 S/cm. The chemical synthesis of graphene, via              be prepared by exposing a metal to various hydrocar-
     the reduction of graphene oxide (GO), is a methodol-              bon precursors at high temperatures. The mechanism
     ogy that has the advantage of having high yields and              of formation of graphene depends, in detail, on the
     ample opportunity to carry out the process on a large             growth substrate and generally begins with the growth
     scale. However, the quality of the chemical synthesis             of carbon atoms that nucleate on the metal after the
     product is rather poor, due to a partial reduction of the         decomposition of hydrocarbons and the nuclei subse-
     GO and an abundance of defects in the crystal lattice,            quently grow in large domains. In addition to gaseous
     which makes the product more suitable for applications            hydrocarbons such as methane, ethylene or acetylene,
     that do not strictly require qualitative graphene, such           liquid precursors such as hexane and pentane have
     as ‘use in polymeric composites. In fact, the quality of          also been used7. Transferring the graphene from the
     the material produced cannot be considered high since             growth substrate to one of interest can be quite diffi-
     it contains both intrinsic defects (such as edges or de-          cult due to the chemical inertia of graphene generating
     formations) and extrinsic defects (such as groups con-            defects in the material, just as thermal variations can
     taining O and H). In general, this process is strongly            affect the stability of the material. CVD, generically, re-
     influenced by the choice of solvent, reducing agent (hy-          mains one of the most successful methods for produc-
     drazine monohydrate, hydroquinone and compounds                   ing graphene over a large area even if the process ap-
     containing sulfur), and surfactant, which are combined            pears complex and a high amount of energy is required
     to maintain a stable suspension4.                                 for the execution of the method. Since CVD is a valid
                                                                       candidate for the production of high quality graphene in
     Liquid Phase Exfoliation                                          large quantities, several research groups have focused
                                                                       in this direction. Bae et al8, used a roll-to-roll (RTR) pro-
     Subsequently, around 2008, the method of exfoliation in           cess for the production of 30 inches and subsequently
     the liquid phase was studied, which is based on the use           the technique was applied for the continuous produc-
     of the pressure forces that are generated inside a liquid.        tion of graphene. One of the latest attempts, carried
     Currently, it appears to be a widely used method for the          out in 2015, made it possible to produce high quality
     production of graphene and involves 3 different steps:            monolayer graphene using cold wall CVD with resistive
     1. dispersion in a solvent or surfactant;                         heating, which was also 100 times faster than conven-
     2. exfoliation;                                                   tional CVD9. In conclusion, it can be stated that CVD
     3. purification to separate the exfoliated from the               allows to synthesize graphene on surfaces of several
          non-exfoliated material and, if supplied in powder           square centimetres, obtaining high crystalline quality
          form, to completely remove traces of solvent5.               (large crystalline grains, low presence of contaminants
     Powdered graphite is mixed with a solvent with specif-            and defects and continuity of surfaces), being able to
     ic physical qualities such as surface tension and / or            easily transfer the material produced. on a wide range
     viscosity or in a mixture of water and surfactant. The            of substrates for different applications.



16                                                                                       Annali di Stomatologia 2020; XIII (1-4): 15-20
M. Covelli et al.

Additional Techniques                                                 ing a potential to graphite bars used as electrodes in a
                                                                      conductive solution, which gradually flake off and gener-
There are also graphite thermal exfoliation techniques                ate graphene nanosheets in solution. The most signifi-
that almost completely provide single-layer graphene                  cant advantage of this method is that it allows to produce
as a product. These are methods that have many ad-                    graphene with modulable properties simply by changing
vantages over mechanical exfoliation: first of all the time           the starting material and the process conditions. Conse-
required to complete the process. In fact, high tempera-              quently, graphene can be tailor-made, depending on the
ture exfoliation processes can last even a few seconds.               specific application10.
In addition, most thermal exfoliation methods produce                 Below in Table I the summary of the advantages and dis-
graphene in a gaseous environment, thus avoiding the                  advantages of graphene production techniques.
use of liquids. When graphite oxide is used as a pre-
cursor, thermal exfoliation simultaneously leads to the
                                                                      Product Evolution: Application of Graphene
reduction of graphene. During heating, the functional
groups bonded to the graphite layers decompose and                    The extraordinary properties of graphene, including its
produce gases that generate pressure between adjacent                 conductivity, transmittance, flexibility and strength, allow
layers. Exfoliation takes place when the pressure ex-                 it to be used in various applications such as electronics,
ceeds the attractive forces between the layers. For this              composites, membranes and next generation renew-
reason, graphite oxide, expanded graphite and graph-                  able energy technologies (e.g. solar cells). Specifically,
ite intercalation compounds are preferably used as raw                however, among the emerging nanomaterials used for
materials for thermal exfoliation instead of simple graph-            biomedical applications, graphene-based biomaterials
ite. In addition to the mechanical, chemical and thermal              have attracted a lot of scientific and technological inter-
methods described above, there are other more recently                est in recent years, showing great future prospects as
developed methods which are equally promising. The                    antibacterial agents, biosensors, bioimaging tools and
electrochemical method, for example, consists in apply-               as components of engineering. of stem cells and tissues.




Table I. Advantages and disadvantages of graphene synthesis and production techniques
 Synthesis techniques                  Advantages                                       Disadvantages
 Top down
 1. Mechanical exfoliation             - Simple method                                  - Not suitable for business and
                                                                                          industrial production
                                       - Easily accessible
                                                                                        - Inability to increase the process.
                                       - Suitable for graphene flake insulation
                                       - It allows to produce graphene crystals of
                                         the highest quality
                                       - Suitable for basic and laboratory
                                         research
 2. Chemical reduction of              - Very high yield                                - Very poor quality of the product
    graphene oxide (GO)
                                       - Possibility of carrying out the process on     - Synthetic product suitable only for
                                         a large scale                                     applications that do not require a
                                                                                           qualitative graphene.
 3. Liquid phase exfoliation           - Synthesis of excellent material                - Very small side dimensions of the
                                                                                          product
                                                                                        - High costs for the use of reactive
                                                                                          solvents
                                                                                        - Not very ecological process
 4. Thermal exfoliation                - Very fast processing times                     - Product not of excellent quality

                                       - Gaseous and non-liquid environment
 5. Electrochemical                    - High quality product
    exfoliation
                                       - Considerably higher yield
                                       - Ecological choice
                                       - Production of graphene with modulating
                                         properties.
 Bottom-up
 1. Chemical vapour                    - Useful for preparing high quality              - Very complex process
    deposition (CVD)                     structural graphene
                                                                                        - High energy quantity
                                       - Easy material transfer on a wide range of
                                         substrates.



Annali di Stomatologia 2020; XIII (1-4): 15-20                                                                                       17
     Graphene: excursus of the evolution of processes and products

     Antibacterial Agents                                            molecules and improve selectivity13. In 2017, a new bio-
                                                                     sensor was reported, specific for the detection of human
     Around 2016, an all Italian research obtained promising         papillomavirus (HPV), where the graphene-polyanalin-
     results aimed at designing nanomaterials for new an-            ia (G-PANI) electrode is modified using a pyrrolidinyl
     timicrobial therapies. This research analyzed the anti-         nucleic acid probe (anthraquinone-labeled peptide)
     microbial effects of graphene oxide on various human            and printed with the inkjet printing method. And it is
     pathogens such as: E. coli, C.albicans, E.faecalis and          through electrostatic attraction that the response of the
     S.aureus. The scholars have evaluated how coating               electrochemical signal on the synthetic oligonucleotide
     medical instruments with this material can help reduce          target is measured14. Promising results were shown in
     infections, especially after surgery, also allowing to re-      the same year by studying and creating graphene mi-
     duce the use of antibiotics. Initially, the studies were        croelectrodes integrated with bilayer lipid membranes.
     very contradictory in this regard, but the Italian team         Under these conditions the biosensor achieves good
     analyzed how the size and concentration of graphene             reproducibility, reusability, high selectivity, fast re-
     oxide sheets affect its antimicrobial action on import-         sponse times, long life and high sensitivity. In addition,
     ant human pathogens. This effectiveness depends on              the use of graphene microelectrodes in the detection
     its size, the agent’s exposure to the material and other        of various toxic substances such as toxins, diagnosis
     parameters; examining the graphene oxide in sheets              of D-dimers, urea and cholesterol has been reported15.
     of about 200 nanometers it was studied how, in aque-            As a consequence of these promising results, in 2020
     ous solution it is able to eliminate about 90% of S. au-        a biosensor made on field effect transistors was pre-
     reus and E. faecalis, and about 50% of E. coli in one           sented, that is, a graphene-FET used to detect clinical
     time equal to about two hours. It was explained how             samples of SARS-CoV2 through the spike protein, with
     graphene oxide sheets can cut bacterial membranes               promising results. These devices exploit the change in
     acting almost like a “nano-knife”, they can envelop bac-        surface potential induced by binding to biomolecules.
     teria and block their growth or oxidize the cellular com-       When some charged molecules bind to the gate they
     ponents of bacteria. The action against the C. albicans         change the charge distribution in the semiconductor
     fungus was also discovered, with an efficacy similar to         and this results in a change in the conductivity of the
     E. Coli. In addition, the possibility of mixing graphene        transistor. Typically, these Bio-FETs include the classic
     oxide with different biocompatible polymers was evalu-          FET structure with source, drain and gate to which the
     ated to obtain an antibacterial coating suitable for med-       sensitive biological element is added, often a film with
     ical devices susceptible to bacterial colonization11. Sub-      binding sites for the analyte. In this new technology the
     sequently in 2019 Elia et al12, studied a nanotechnology        basic operation is the same as the classic FET but a
     strategy consisting of graphene oxide or carbon nano-           thin graphene channel, tens of microns thick, has been
     fibers (CNF) combined with the irradiation of light-emit-       added between the electrodes of the two main compo-
     ting diodes (LEDs) as novel nano-weapons against two            nents. Typically, graphene behaves as an inert material
     Gram-positive pathogens. multidrug-resistant, clinically        but under certain conditions it can absorb different mol-
     relevant: methicillin-resistant Staphylococcus aureus           ecules and bind easily, this allows the graphene-FET
     (MRSA) and methicillin-resistant Staphylococcus epi-            to be functionalized with biologically sensitive systems
     dermidis (MRSE). Several tests and studies on other             such as enzymes, DNA, RNA or antigens16.
     pathogens such as viruses, fungi and other resistant
     bacteria are still ongoing.                                     Bioimaging

     Biosensors                                                      Around 2014, graphene quantum dots (GQDs) were first
                                                                     defined as a new class of fluorophores17. The GQDs
     In biomedical applications, graphene-based nano-                showed great photophysical properties and good bio-
     structures with highly sensitive and selective perfor-          compatibility, with characteristics very similar to a mol-
     mance as biosensors have recently been reported.                ecule compared to other quantum dots, therefore to be
     The studies concerning this specific applications date          used in various applications of life science and in bio-
     back to the period 2015-2017 up to 2021 with studies            medicine. Until before, all the fluorophores used in bio-
     on graphene-based biosensors for the detection of               imaging were organic dyes with not very relevant char-
     COVID-19. Graphene is a semi-metal with ultra-high              acteristics such as the tendency to photo-bleaching.
     charge mobility capable of offering excellent electronic        On the contrary, GQDs have unique optical properties
     properties and of being functionalized on its surface,          directly linked to their shape, size and surface chem-
     and it is for these reasons that graphene-based mate-           istry, so that they are considered suitable for bioim-
     rials have been exploited in bio-sensing applications.          aging. In addition, even with femtosecond laser (NIR)
     The functionalized area of graphene is able to direct-          excitation in the near infrared, GQDs show very little
     ly detect the biomolecules from its oxide components            photo bleaching. Their small size allows them to easily
     due to the synthesis in which many epoxide, hydroxyl            cross biological barriers, targeting specific areas and
     and carboxyl groups are formed on the edges and on              anatomical regions that are difficult to access18. Over
     the surface sites. In addition, functionalized graphene         time, several in vivo and in vitro studies have made it
     allows the binding of heteroatoms, antibodies, en-              possible to know the different characteristics and ca-
     zymes, DNA, proteins and several specific molecules.            pabilities of GQDs. In fact, in 2015, Kumar et al19, syn-
     Graphene provides a high possibility of active sites for        thesized functionalized green GQDs, highly biocom-
     charge-biomolecule interactions thanks to the large             patible with dimensions between 3 and 14 nm through
     specific surface area that leads to improved detection          the acid treatment of graphite powder. In vivo studies,
     and supports the desired functionalization to target bio-       on the other hand, date back to very recent times



18                                                                                    Annali di Stomatologia 2020; XIII (1-4): 15-20
M. Covelli et al.

thanks to the fact that many researchers had carried         cial neural implants. The first studies were conducted at
out studies on nanoparticles of 40 nm and therefore          the University of Manchester and the Catalan Institute
of the same size as GQDs. In recent times, however,          of Nanosciences and Nanotechnology in Spain, where
Fan et al20, have exploited the lower Ph of solid tumors     graphene and related materials were examined for the
compared to that of normal tumors, therefore a pH of         design of devices for neural implants to record and stim-
6.5 compared to a pH of 7.0-7.4. pH -sensitive GQDs          ulate electrical activity in conjunction with a targeted ad-
were prepared capable of changing their emission             ministration of certain drugs. These neural implants ap-
from green (pH <6.8) to blue (pH> 6.8). These GQDs           pear to be a very promising approach for the detection,
were injected subcutaneously into tumors and adja-           monitoring and treatment of a range of different sensory
cent muscles in mice carrying various tumors, such as        and motor disorders of the central and peripheral ner-
glioblastoma multiform. Evaluated the images under           vous systems.
the microscope, after 24 hours it was shown how the          These implants have the function of creating a connec-
tumors emitted green light and the muscles blue light.       tion and interaction between neural tissue, nerve fibers
The ability of GQDs to reach tumor regions by measur-        or individual neurons and external devices, used to re-
ing fluorescence was tested by intravenous injection.        cord, monitor and stimulate brain activity to intervene
It was possible to see how quantum dots successfully         in the functions of the central nervous system. Start-
crossed the blood brain barrier, being able to classify      ing from this, it can be said that graphene is a versatile
them as potential probes for fluorescence-guided can-        substrate that can take different shapes with different
cer surgery but also for diagnosis.                          properties and proves to be excellent for generating 2D
                                                             materials used for stimulation and recording devices.
Stem Cell and Tissue Engineering                             Monolayer graphene nanosheets facilitate the recording
                                                             of electrical activity in neuronal tissue, while reduced
In the field of regenerative medicine and tissue engi-       graphene oxide has been selected for electrical stimu-
neering, graphene has been regarded as a versatile           lation of the nervous system, capable of providing stim-
“nano-platform”. The application of graphene in this         ulation for long periods. This research group also looked
context of biomedicine is to be associated with mod-         at the technology to develop a retinal implant for people
ern times, starting from 2019 onwards. In fact, in 2019,     who have lost their lives due to retinal diseases. In addi-
Jagiello et al21, demonstrated the impact of graphene-       tion, graphene can be modulated and functionalized with
based substrates (reduced graphene oxide and oxide)          oxygen allowing the administration of anti-inflammatory
on the biological properties of mesenchymal / stromal        drugs and neurotransmitters released at different rates
stem cells. Their results underline that both graphene       after implantation, thanks to the hydrogel coating of the
oxide and reduced graphene oxide-based scaffolds             graphene sheets. Hence the research for the biomedi-
show potential applicability as novel, biocompatible,        cal applications of graphene and 2D materials has ex-
safe materials for use in biomedicine. In 2020, howev-       panded into various fields, even reaching the diagnosis
er, other studies made it possible to combine graphene       of cancer25.
with bioceramics to recreate a 3D printable scaffold
                                                             Conclusions
with specific characteristics for bone regeneration, also
studying how carbon affects cell proliferation and dif-      In conclusion, graphene thanks to the structure made
ferentiation in vitro. Through this study it was proposed    of carbon atoms has extraordinary properties hence the
to add carbon-based material for a new biocompatible         name “material of wonders” or even “miraculous mate-
3D scaffold that could become the key structural ma-         rial”. Graphene has a higher resistance than steel and
terial for bone regeneration22. Also in the same year it     a somewhat unique electronic and thermal conduction
was shown how a graphene oxide scaffold stimulated           capacity. Looking towards the future, research and in-
the proliferation of myogenic progenitor cells and en-       dustry need to collaborate to drive innovations and di-
docrine functions of differentiating cells, thus actively    rect research towards the most promising applications
participating in the construction of muscle tissue23. In     also from a commercial point of view, evaluating the
addition, in the same year, studies were carried out on      significant progress that has been made in the last 8-9
the potential application of graphene oxide in the man-      years. The most promising discoveries as seen in the
ufacture of electrodes for retinal prostheses, used for      previous sections were those in the field of engineer-
retinopathies. Graphene was chosen as the material           ing and regenerative medicine thanks to the physical,
for the electrodes due to its superior chemical-physi-       chemical and biological properties of graphene, paying
cal characteristics compared to other materials. These       particular attention to its use as a vehicle for the deliv-
prostheses provide excellent assistance in the treat-        ery of genes / drugs. It is also expected that, thanks
ment of age-related macular degeneration (AMD) and           to the combination of graphene (but also derivatives)
retinitis pigmentosa. From here we can understand how        with other compositions, the future possibility of gener-
this specific material can be applied in the field of cell   ating and manufacturing new intelligent and multifunc-
and tissue regeneration associated with nanotechnolo-        tional materials. It is obvious that this biomaterial is not
gies and electrical and electronic engineering24.            only positive but also problems related, above all, to
                                                             cytotoxic and genotoxic effects. At the moment there
Applications in the Neural Field                             is no gold standard to overcome the problems asso-
                                                             ciated with graphene, it is thought, in fact, to continue
Health services require more and more innovative solu-       with more in-depth investigations on this material and
tions to meet the growing demands and graphene in            its derivatives by developing new experimental models
2018 paved the way in the treatment and management           on which to base before proceeding with further clinical
of diseases of the nervous system with the help of spe-      applications.



Annali di Stomatologia 2020; XIII (1-4): 15-20                                                                              19
     Graphene: excursus of the evolution of processes and products

     Informed Consent Statement: Not applicable.                      14 Prinjaporn T Weena S Adisorn T Charles SH Tirayut V
                                                                          Orawon C Electrochemical paper based peptide nucleic
     Conflicts of Interest: The authors declare no conflict               acid biosensor for detecting human papillomavirus Anal
     of interest.                                                         Chim Acta 2017; 952: 32 40
                                                                      15 Nikoleli G P ; Siontorou C ; Nikolelis D ; Bratakou S ;
                                                                          Karapetis S ; Tzamtzis N Biosensors Based on Lipid Mod
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20                                                                                       Annali di Stomatologia 2020; XIII (1-4): 15-20
