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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 2  |  Issue : 2  |  Page : 21-24

Graphene – Scope in conservative dentistry and endodontics


Department of Conservative Dentistry and Endodontics, New Horizon Dental College and Research Institute, Bilaspur, Chhattisgarh, India

Date of Submission01-Feb-2021
Date of Decision16-Feb-2021
Date of Acceptance01-Mar-2021
Date of Web Publication24-Jun-2021

Correspondence Address:
Priyankita Kar
Department of Conservative Dentistry and Endodontics, New Horizon Dental College and Research Institute, Sakri, Bilaspur - 495 001, Chhattisgarh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpcdoh.jpcdoh_11_21

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  Abstract 


Graphene, a member of the carbon family, is the strongest, stiffest, and thinnest known material, with a thickness of 10 nm. It has emerged as engineered nanomaterials and nanomedicines in dentistry with promising results. Usually produced employing Hummers method, graphene possesses excellent physiomechanical properties, electrical conductivity, stability, biocompatibility, and biodegradability. Owing to their interactions with dental pulp stem cells, they have been functionalized with many scaffolds in regenerative dentistry, to upregulate the odontogenic and osteogenic genes. This emerging science of graphene-based materials has also been used for the debridement of root canals. Their unique property of antibiofilm and antiadhesiveness has been used to prevent dental caries and erosions. In addition, they have been incorporated into various biomaterials to enhance their original properties, like in glass ionomers, biodentine, and in bleaching agents like hydrogen peroxide. Depending on their concentration and time of exposure to the substrate, graphene and their derivatives can be effective antibacterial agents. This updated review provides useful information on the promising introduction of graphene in the field of conservative dentistry and endodontics.

Keywords: Biomaterial, bleaching, carbon family, recent advances, tissue engineering


How to cite this article:
Kar P, Varghese RK, Agrawal N, Jhaveri HS. Graphene – Scope in conservative dentistry and endodontics. J Prim Care Dent Oral Health 2021;2:21-4

How to cite this URL:
Kar P, Varghese RK, Agrawal N, Jhaveri HS. Graphene – Scope in conservative dentistry and endodontics. J Prim Care Dent Oral Health [serial online] 2021 [cited 2021 Oct 23];2:21-4. Available from: http://www.jpcdoh.org/text.asp?2021/2/2/21/319191




  Introduction Top


Advancements in biomaterials and their growing clinical applications have recently led graphene to gain much attention. Graphene, a carbon allotrope, having two-dimensional, single, sheet-like, honeycomb pattern arrangement, has extremely high mechanical strength and young's modulus. Its use in dentistry is in accordance with its chemical, thermal, structural, and biological properties. Graphene nanomaterials comprise few-layer graphene, graphene nanosheets, graphene oxide (GO), and reduced GO.[1] Among these, GO is the most important derivative of the graphene family, which is produced by the energetic oxidation of graphite employing the Hummers method. They contain numerous chemically reactive functional groups on its surface, facilitating their binding with materials such as biomolecules, DNA, proteins, and polymers.[2] GO can be reduced chemically, electrochemically, and thermally to produce reduced GO.[3] An advancing member of this graphene family is the fluorinated graphene, which has favorable biocompatibility along with exhibiting neuroinductive effect through spontaneous cell polarization. It also enhances the proliferation of mesenchymal cells to provide a scaffold for their growth. However, studies in dentistry are limited as compared to their research in the medical field.


  Brief History Top


Hummers prepared graphite oxide in 1848, which was again introduced by Brodie et al. in 1958. In 1962, reduced GO was produced by reducing graphite oxide. Boehm et al. proposed the term graphene to illustrate and describe the single-layer structure of graphite-like carbon in 1986. Multiple layers were isolated by micromechanical exfoliation in 1999 by Rouff et al. and in 2004, Geim and Novoselov isolated single layer of graphene by mechanical exfoliation, for which they received a Nobel prize in 2010.


  Preparation of Graphene Oxide Top


The physical properties of GO are different from pure graphene as most of the carbon atoms in the former are covalently connected to oxygen atoms. Usually, three methods are employed to prepare GO: Brodie's method,[4] Staudenmaier's method,[5] and Hummers' method.[6] The method used for production determines the number and types of oxygen functional groups in the final product, which further determines their physical properties. The most common method adopted and reported in recent years is the Hummer's method.

Hummer's method requires 100 g of graphite, 50 g of sodium nitrate, and 2.3 L of sulfuric acid, to be stirred along with cooling. To this mixture, 300 g of potassium permanganate is slowly added, during which it is necessary to maintain the temperature below 20°C. Then, it is left to stand in a 35°C water bath for 30 min, following which 4.6 L of water is added. Now, it is heated in a 98°C water bath for 15 min and the mixture is diluted by adding water up to 14 L. To this mixture, hydrogen peroxide in a solution form is added until the bubbling stops. With the aid of filtration and washing, the impurities are removed.


  Biological Properties of Graphene Top


Biocompatibility

Increasing popularity of graphene and their nanomaterials in dentistry have necessitated clinical and laboratory biocompatibility studies. Although in vivo studies are limited, it is almost certain that the hydrophilic forms are more biocompatible than the hydrophobic forms. Furthermore, reduced GO is less toxic than GO.[7] In a study by Rosa et al., they concluded that the GO-based substrates when used, not only permitted the stem cell attachment and proliferation but also upregulated the mineral-producing cells.[8] A biocompatibility study by Dreanca et al.[9] evaluated the renal and hepatic toxicity and found no changes in the weights of organs and the tissue-specific enzymes remained within the normal limits of the species. They also prepared an experimental restorative material which presented with slight inflammatory response and some oxidative stress.

Antibacterial activity

This property depends on the material's concentration, exposure time, and its physiochemical properties.[10],[11] Graphene nanocomposites demonstrate the excellent antibacterial activity by physically damaging the microorganisms by penetrating and breaking the cell membranes, along with wrapping the cells to induce mechanical stress and by extracting phospholipids from lipid membranes. It is also capable of producing oxidative stress. They also get inserted into bacterial membranes, breaking the Van der Waal's forces. The hydrophobic nature results in the extraction of phospholipids from the lipid layers of the bacterial membranes. These irreversible damages make graphene very effective antibacterial material.[12],[13],[14],[15],[16] Beneficial, as it seems, this antibacterial is all relative and is questionable to be generalized.

Biodegradability

The fate of graphene in vivo can be determined by how it is degraded. Several studies and investigations have concluded that neutrophils are capable of degrading highly dispersible graphene.


  Potential Uses of Graphene in Conservative Dentistry and Endodontics Top


The exclusive properties of GO have inspired researchers to apply it in the prevention of dental caries and biofilm adhesion, along with its addition to materials such as glass ionomer cements, biodentine, and hydrogen peroxide, to enhance their properties. They have been tried and tested as an adjunct to chemical debridement of root canals and tissue engineering.

Restorative dentistry

Although the latest advancements in glass ionomer cement constitute the incorporation of different fillers such as hydroxyapatite, metallic powders, and fibers, its poor physiomechanical properties continue to be a concern. Of late, attempts have been made to integrate graphene-derived nanomaterials into commercially available glass ionomer cements to enhance their reinforcement. The resultant product has significantly improved physical and mechanical properties than glass ionomers. The addition of fluoride graphene (FG) to glass ionomer could produce a GICs/FG composites matrix, that could augment the mechanical as well as antibacterial properties. This combination also decreases the pores and microcracks in the material's internal structure, along with increasing the antibacterial property, which makes it less susceptible to microbial invasion and erosion disintegration. Graphene nanoparticles can also improve the physiochemical properties of resin polymer matrices. Bregnocchi et al. proposed in their esteemed study, using graphene family nanoparticles with dental adhesives to provide antimicrobial and antibiofilm properties. Their study demonstrated that the experimental modified dental adhesive suggestively subdued the adhesion and growth of Streptococcus mutans. This was achieved without manipulating its original mechanical properties and without producing excess of reactive oxygen species.

Endodontics

Persistent infection is the chief cause of failure of endodontic therapy. Photodynamic therapy has lately gained importance for effectively disinfecting canals while preserving dentin structures. In this technique, a nontoxic photosensor, namely indocyanine green (ICG) plays a major role, but it has some drawbacks like its concentration-dependent aggregation and instability.[17] By modifying ICG with GO, a significant reduction in the population of Enterococcus faecalis was observed, along with improvement in its bioavailability, stability, and prevention of degradation.[18] A novel root canal irrigant which incorporates graphene into silver nanoparticles showed similar efficacy as 3% sodium hypochlorite solution and exhibited less cytotoxicity to the bone and soft tissues than the latter.[19] Graphene nanosheets can also be added to some bioactive materials, like Biodentine and Endocem Zr, to decrease their setting times.[20] Singh et al.[21] developed a novel root canal obturating material made up of polymer nanocomposites incorporating GO and found that it had improved antimicrobial activity and mechanical properties than commercial Gutta Percha, and reportedly non-toxic to neighboring cells.

Tissue engineering

Rosa et al. were the first to confirm the ability of GO to allow dental pulp stem cells attachment and their proliferation in 2016.[8] This was followed by Xie et al. who attempted to induce DPSC's osteogenic and odontogenic differentiation by GO produced by chemical vapor deposition. It downregulated the expression of odontoblastic genes such as Dentin Matrix Protein, Pax, and Msh homeobox 1, without any bioactive stimuli. This suggested that graphene grown using chemical vapor deposition may not be suitable as a platform for endodontics and pulp regeneration. On the other hand, osteogenic proteins, and genes such as osteocalcin, COL (collagen), and runt-related transcription factor 2 (RUNX2) were upregulated by graphene. Nonetheless, it could be a potential biomaterial for osseous engineering and regeneration, while presenting to be the most promising biocompatible scaffolds for mesenchymal stem cell's adhesion, proliferation, and differentiation.[21],[22]

In a recent study by Jae Ahn et al.,[23] synthesized mesoporous bioactive glass nanoparticle (MBN) composite with GO to study the ability to mineralize and the differentiation potential of human dental pulp stem cells (hDPSCs). Their results showed enhanced effects on the mRNA and protein expression of odontogenic differentiation markers in hDPSCs and even promoted the mineralization which is deemed to be an essential step for regeneration of dentin. They concluded that this MBN/GO composite can therefore be used in dentin-pulp complex tissue engineering. Ahmad Gholami et al.[24] synthesized chitosan functionalized GO and carboxylated graphene and found that the latter was safer with higher cytocompatibility when exposed to hDPSCs. Negar Mansouri et al.[25] fabricated GO/sodium alginate (GOSA) and reduced GOSA scaffolds, which proved to have controlled biodegradability and surface cell adhesion, thus aiding in the superior proliferative ability of hDPSCs.

Bleaching

Graphene, when paired with appropriate materials, has proved to improve teeth whitening. A nanocomposite was developed employing reduced GO and cobalt tetraphenylporphyrin to be used as a catalyst for bleaching of teeth.[26] This compound when used with hydrogen peroxide using standard photoactivation, increased the bleaching effect of the latter, along with reducing the treatment time. It was seen that when both the components were photoactivated together, it created more chemical reactions between the stain molecules on teeth and hydrogen peroxide.[7]

Drug delivery

GO incorporated in titanium implants has proved to be a promising drug delivery method in biomedical and pharmaceutical applications.[27] This property can be utilized in endodontics for intracanal medicament as nanosheet structures, with high surface area and good water dispersibility. However, studies on drug delivery in dentistry are limited.


  Challenges Top


Despite abundant studies on graphene and its derivatives, it is at an early stage of research and development, calling for some significant challenges to be addressed. A key challenge is its long-term biocompatibility issues in the clinical scenario.[28],[29] In a recent study, it was reported that graphene's purity should be taken into consideration during biofunctionalization procedures as graphene-based materials might produce oxidative debris, which may lead to cytotoxicity.[29] Before the commercialization of graphene-based materials, toxicity profiles, biodegradability, and biocompatibility must be considered at large, with parallel considerations into cost-effectiveness and production reliability.


  Conclusion Top


Graphene and its derivatives have been applied in all fields of medicine; however, in dentistry, they have been a few steps back. Graphene, the strongest, stiffest, and thinnest imaginable material, provides unique properties such as superior physiomechanical properties, large surface area, and their ability to amalgamate with different substances, to augment their properties. This carbon-derivative material can be used to fabricate biocomposites and to enhance the bioactivity of the existing biomaterials, providing progressive and promising dimensions in the field of dentistry in the days to come.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Introduction
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