Application of Graphene: A Nanostar in the World of Dentistry

Introduction

The scientific world is transforming with the discovery of new materials; nanoforms are taking the rule nowadays. Graphene has emerged as a novel and potential nanoparticle that has exceptional properties. It is unique in being the thinnest and strongest material in existence. It is composed of two-dimensional sheets of less than 10mm thickness.¹ Graphene has various applications in varied fields. It is used in supercapacitors, wireless powers, energy storage, and nanoscale transistors for water filtration and desalination. In the biomedical field, it is used in DNA detection, drug delivery, detection of bacteria, cancer therapy,² biosensing and bioimaging, photothermal therapy ³, and in dentistry.

Graphene was discovered by Andre Geim and Konstantin Novoselov at the University of Manchester in 2004.2 Graphene is produced by mechanical or chemical exfoliation of graphite via chemical vapor deposition. It is considered hydrophobic because of the absence of oxygen groups.⁴

Graphene-related materials can be classified either on the number of layers (eg. mono- or multi-layered) or their chemical modification into:

1. Graphene oxide (Figure 1) (GO)

2. Reduced graphene oxide (rGO)

3. Nitrogen-doped graphene (N-G)

The various forms of graphene are:

a) Graphene nanoplates

b) Graphene nanoflakes

c) Graphene powder

d) Graphene thin sheets

e) Graphene foam²

In this paper, the applications of graphene as a reinforcement material in dentistr1y and its properties as a novel nanomaterial are mentioned.

Graphene in denture base materials

Polymethylmethacrylate (PMMA) is one of the most commonly used denture base materials.⁵ There are certain drawbacks of this material for which nanoparticles have been incorporated to enhance those properties. These are:

• Mechanical properties
• Antimicrobial property
• Thermal and electrical properties⁶

A variety of reinforcing agents in the form of cobalt-chromium wires, metallic wires, polyamide fibers, carbon fibers, ultra-high molecular weight polyethylene, and varying amounts of powdered silver, copper, aluminum, and ceramic fillers have been added previously to PMMA.⁷

Recently, graphene has emerged as a potentially useful nanofiller that is gaining research interest due to its exceptional properties. Various studies have been conducted to test the properties of PMMA after the incorporation of graphene (Table 1).

Thus the experiments suggest that GO incorporated PMMA significantly improved the mechanical and thermal properties of PMMA and also has antimicrobial and anti-adhesion characteristics.6 Graphene oxide (GO) has proven to be an anti-quorum sensing agent which is why it is an effective anti-biofilm addition to PMMA.¹²

Research is needed to further evaluate the bonding of teeth with GO/PMMA resin dentures, the effect on impact strength after GO incorporation, and the intraoral evaluation of the anti-biofilm effect.

Graphene in restorative materials:

Restorative cement, crowns, and endodontic materials have been reinforced with various materials over the years to improve their properties.. Antibiotics, quaternary ammonium compounds, and chlorhexidine have been used as reinforcing agents in glass ionomer cement or zirconia and alumina in bioactive cements to improve certain mechanical properties.. Graphene being an exceptional nanofiller has recently gained importance to be incorporated into these materials without compromising the overall performance of the material(Table 2).^13,14  

Graphene in tissue engineering

Bone regeneration plays an important part in regenerative dentistry. Human dental pulp stem cells (hDPSCs) are used for tissue engineering as they secrete a dentin matrix and have the capability to differentiate into odontoblasts.²¹ Recently, bioactive glass (BAG) has been used as a biomaterial for dentin regeneration due to its capability of releasing ions and resorbable properties. But BAG lacks adequate mechanical strength and is not sufficient for heavily loaded environments. Bioactive ceramics such as mesoporous bioactive glass nanoparticles (MBNs) have weak mechanical properties, are highly brittle, and have low tensile strength. Certain polymers and inorganic materials have been found as reinforcement materials to enhance the mechanical strength of these materials.

The incorporation of graphene into these was done in a few in vitro studies. It was found that graphene increased the proliferation of human mesenchymal stem cells (MSCs) and there was no sign of cytotoxicity.²² Graphene can also be incorporated into membranes for guided bone regeneration (GBR) done in dentistry. The role of graphene in driving the osteogenic differentiation of stem cells has been evaluated through many studies as mentioned in Table 3.

Graphene has been used recently in tissue engineering field to enhance and improve the biocompatibility, spacemaking, clinical manageability, and tissue integration of the various membranes and grafts used.²²

Graphene in esthetic dentistry

Teeth whitening is a procedure that has gained importance recently. It is done using hydrogen peroxide (H₂O₂ ) based materials. The risk factors of tooth whitening are dentin sensitivity, gingival irritation, and changes in tooth microstructure which depend on the concentration of H₂O₂ and the duration of the treatment.

Su and co-workers experimented with rGO and cobalt tetraphenylporphyrin (CoTPP) as catalysts for tooth bleaching to overcome these risks. It was found that H₂O₂ plus rGO/ CoTPP under photoactivation increased the whitening effect of peroxide and decreased the treatment time further decreasing the risks involved in the treatment.²²

Graphene as antibacterial and anti-demineralization material

Demineralization of dentin is an irreversible loss of tooth structure which further leads to pain and hypersensitivity. Many agents have been used to treat the demineralization of dentin such as fluoride and oxalate-based materials. The major drawback of these is that they cause discoloration of dentin.

Graphene as an anti-demineralization agent:

Graphene oxide has been tested to evaluate its potential to prevent the demineralization of dentin by covering its surface and sealing the orifices of the dentinal tubules. GO along with 5 different f-GO-nanocomposites were synthesized in a study done by Nizami et al. (2019) and its effect on the prevention of demineralization of dentin was seen. It was found that f-GO-nanocomposites were stronger against demineralization than other agents used before and led to lesser or no color change of dentin, proving it to be a better material. Hence, f-GO-nanocomposites were suitable for the prevention of tooth decalcification caused by cariogenic microbes.²³ 

Graphene as an antibacterial agent:

Hu et al. were the first to discover the bactericidal effect of graphene-based materials against Escherichia coli. The activity of graphene against Streptococcus mutans in both planktonic and biofilm forms was evaluated by Zhao et al. (2020). In the study, it was found that GO nanosheets had an antibacterial effect on S.mutans in both forms in a concentration-dependent manner. Their antibacterial activity was through oxidative stress damage. Thus, GO could be a potential additive in dental restorative materials preventing the adhesion of bacteria.²⁴

He et al. mentioned that GO had a strong antibacterial effect on dental pathogens including S.mutans. He evaluated the effect of GO nanosheets against S.mutans, Porphyromonas gingivalis and Fusobacterium nucleatum . ²⁵

So, the antibacterial effect of GO is prominent and with increasing concentration, it has a more enhanced effect on suppressing the viability of pathogens. But the effect of GO could be altered by some factors like saliva, electrolytes, and proteins. So, further studies are needed to have a better understanding of the properties of GO in preventing caries.

Graphene in dental implants

Dental implants are made with various surface modifications to enhance osseointegration and suppress biofilm formation to prevent peri-implantitis. Recently, graphene has been used for coating titanium implants to evaluate its benefit in osseointegration and as an antibacterial agent. Various studies that have been undertaken are mentioned in Table 4.

Various types of graphene including GO and rGO have been proven to have greater diffusion and stability and their potential to be used as a coating for implants is also prominent. But further in vivo research and evidence are required for graphene to be used as a promising material in implantology.²³

Graphene in oral cancer treatment

It is important to check the risk factors of oral cancer and get it diagnosed at the earliest to help prevent its spread. Resistance to conventional therapeutic approaches by cancer stem cells (CSCs) or tumor stimulating cells has been observed. Various studies have suggested that GO can be delivered as a therapeutic agent for targeting CSCs at the location of the tumor. GO has an inhibiting effect on signal transduction pathways.²

Various studies have been done to evaluate graphene for cancer therapy. They are enlisted in Table 5.¹²

Limitations, scope, and future perspectives

Graphene is in its early stage of research and a few challenges are still there which need to be addressed before it is widely commercialized as a dental material. Several reports have mentioned that the behavior of graphene and its derivatives and their toxicity depends on the physiochemical properties of the structure.¹ One of the major goals for the biomedical application of graphene as an antibiotic agent is based on the understanding of its toxicity profile. We must investigate the cost-effectiveness, reproducible synthesis, and stability of these nanomaterials for use in dentistry. Graphene-based nanomaterials (GBNs) must undergo more clinical trials to check their safety and efficacy of them, which will further dictate their use in this field.¹

As graphene is still in its infancy stage, there is a need for proper future research to change the material into a market-oriented research area. However, it provides great avenues for further development in the applications of graphene.⁴

Conflict of interest

None