Graphene: A Boon In Dentistry

Introduction

The term graphene was recommended by the relevant IUPAC Commission to replace the old term graphite layers. Graphene is a newly invented material that was discovered by Andregeim and Konstntin N at the University of Manchester in 2004. They are awarded by Nobel prize in 2010 for this invention.¹ Graphene is a single two-dimensional layer (less than 10 nanometers) in which the carbon atom is bounded with three more carbon atoms with SP2 hybridization and organised in a hexagonal mesh-like structure. The inner layer is arranged through Vonderwall forces which are responsible for the softness of the material (Figure 1).^1,2

Graphene family Nanomaterials (GFNs) include:

1.Ultra-thin Graphite 2. Few layers Graphene (FLG) 3. Graphene oxide (GO) 4. Reduce Graphene oxide (rGO) 5. Graphene Nano sheet (GNS) 6. Fluorinated Graphene (FG)

Properties of Graphene

Graphene is a remarkable material with numerous properties which make it highly desirable for various applications. Some of its key properties include biocompatibility, exceptional strength, anti-microbial adhesion characteristics, flexibility, transparency, stiffness, being the thinnest material, complete impermeability, and most stretchable crystal. Additionally, it has high intrinsic mobility and has been found to have teeth whitening properties.

Biocompatibility

Hydrophilic Graphene nanoparticles are believed to exhibit better biocompatibility than hydrophobic graphene nanoparticles. Graphene oxide has some degree of hydrophilicity, which is attributed to the existence of functional groups containing oxygen in its base plane. The toxicity of GFNs within the oral environment is insignificant.² GFNs, specifically GO, caused a concentration and time-dependent rise in intracellular reactive oxygen species (ROS) production. Growth inhibition and changes in mitochondrial membrane potential were observed at a higher concentration of 40 μg/mL.² At concentrations of 4 ug/mL, they exhibit good safety and have a strong antioxidant defense. GO has low cytotoxicity and causes minimal harm to stem cells of human dental follicles.⁴

Strength

According to findings from atomic force microscopy (AFM), it has been determined that graphene is among the strongest materials known. The durability of monolayer graphene is 42 N m-1, Young’s modulus is 1.0 TPa.¹ The surface area–to-mass ratio is very high (2630 m²/g). It’s Young’s modulus, ≈1100 GPa, so it has very high mechanical strength. Thus, graphene has 100 times better mechanical strength than steel.³

Antibacterial effect

The potential of graphene oxide nanosheets to inhibit the growth of different dental pathogens and fungi has been investigated. These pathogens include Streptococcus mutans, Porphyromonas gingivalis, Fusobacterium nucleatum, Xanthomonas campestris pv. undulosa, and Pseudomonas, as well as fungi such as Fusarium oxysporum and Fusarium graminearum. It was found that GO was able to destroy around 90% of the bacteria and impede 80% of the germination process of macroconidia (Figure 2).4 Moreover, GO sheets caused local disruption of the cell membrane of bacteria and fungal spores by interlinking them, leading to partial cell swelling. This interlinking decreased the potential of bacterial membranes and resulted in cell lysis due to the leakage of electrolytes of fungal spores.8 Graphene combined with another compound like zinc oxide Nanocomposite exhibited enhanced anti-microbial antibiotics and anti-adherence activities against oral pathogens.²⁰

Flexibility

Graphene sheets are frequently blended with polymers or inorganic nanoparticles to form composites to improve their flexibility and extend their functions.⁶ Due to its high flexibility the impact forces on the underlying implant body are very low, and the graphene structure acts as a shock absorber. This is a game changer in Implant Dentistry.

Transparency

The absorbance rate of white light with a graphene-single-layer is 2.3% with negligible reflectance. The absorbance increases sequentially with the number of layers from 1 to 5. The transparency of graphene depends on its fine structure constant α = 2pe 2 /hc. Graphene is highly transparent to visible light, that is, 97.7 %¹ which is highly aesthetic for dental prosthesis.

Stiffness

Graphene is the toughest crystal structure of all known materials.

Thinnest material

Graphene is a very light material at 0.77 milligrams per square meter (for comparison purposes, one square meter of paper is roughly 1000 times heavier. One common statement is that a football field-sized single layer of graphene, which is only one atom thick, would weigh less than 1 gram.⁴

Completely impermeable

Graphene is also highly impermeable, and even helium atoms cannot penetrate it.⁶

Most stretchable crystal

Graphene is the most stretchable crystal. We can stretch it up to 20% of its initial size without breaking it.³

High intrinsic Mobility

The electronic mobility of graphene is very high, with formerly pronounced outcomes above 15,000 cm² ·V−1·s−1 and theoretically possible limits of 200,000 cm² ·V−1·s−1 (limited by acoustic phonon scattering). It is stated that graphene electrons act similarly to photons in their mobility due to lack of their mass.²²

Graphene Form

Graphene nanoplates, Graphene nano-flex, Graphene powder, Graphene thin sheets, and Graphene foam.

Using Graphene in Dentistry

Graphene has shown potential applications in various fields of dentistry such as restorative dentistry, denture base material, implant, tissue engineering, and periodontology.

Graphene In Conservative Dentistry

The combination of fluorinated graphene with glass ionomer cement is a very good restoration material.⁴ The fluorinated graphene releases fluoride ions, because of which it has a wide range of applications in restorative dentistry such as restoration of deciduous teeth, and, anterior class 3 and class 4 restorative cementation of crowns, etc. Its combination showed more antibacterial effects on Streptococcus mutants, Staphylococcus aureus without interfering with its unique mechanical performance.³ With the increases in fluoride graphene content in GIC are also known to improve the mechanical properties such as a decrease of pores and micro-cracks in the internal structures of materials susceptible to erosion.

Conventional restorative materials in dentistry, like resin-based composites, adhesives and silane primers, were blended with graphene oxide to confirm the impacts on mechanical properties.¹⁶ The efficacy of functionalized graphene oxide (f-GO) nanocomposites on the decalcification of dentin, like graphene oxide -silver (GO-Ag), GO-calcium fluoride (GO-CaF2), GO-Ag-calcium fluoride (GO-Ag-CaF2), GO-zinc (GO-Zn), and GO-tricalcium phosphate (Ca3(PO4)2). The use of GO-Ag, GO-Ag-CaF2, and GO-CaF2 nanocomposites demonstrate high efficacy in preventing decalcification. In contrast, the application of silver diamine fluoride results in significant discoloration of dentin, whereas f-GO nanocomposites exhibit little or no discoloration.¹⁴

Graphene as denture base material

Graphene is one of the ideal nanomaterials to improve the performance of auto-polymerizing acrylic resin for denture base and dental uses due to its high weight resistance ratio, high traction resistance, coefficient of thermal expansion, high capacity for absorption, lubrication and flexibility.⁷

The application of graphene with auto-polymerizing acrylic resin is improving its mechanical properties, increases the elastic modules and the tenacity, with reduces the appearance of cracks and decreases the shrinkage ratio during the polymerization process.⁸

Tissue engineering

Tissue engineering is a new field in medical life sciences that targets the development of biological substitutes to modify the function of tissue to repair and maintain its properties. These biological substitutes are also known as scaffolds, which are made of biodegradable materials.⁹ However, different tissues in the body possess different mechanical, electrical, and physical properties. Hydroxyapatite [HA; Ca10(PO4)6(OH)2] is commonly used in various forms and shapes for bone tissue regeneration.

Graphene has been used as a scaffold in combination with hydroxyapatite, and other molecules. To improve the release of calcium and phosphorus ions, HAp/GO composites have been combined with chitosan and gelatin.¹⁷ Combining HAp with GO has been shown to improve the adhesion to titanium and increase its resistance to corrosion. Furthermore, this combination improves the material's fracture toughness and elastic modulus.²³

The combination of chitosan and rGO nanocomposites may offer a favorable atmosphere for the growth and attachment of hMSCs. It increases cell-substrate interactions and cell-to-cell contacts and also promotes the osteogenesis and neurogenesis of hMSCs.¹⁶

Periodontal Tissue Regeneration

The destruction of periodontal tissue comprising the periodontal ligament, alveolar bone, and cementum characterizes periodontitis, an inflammatory condition This condition may lead to teeth mobility and several associated disorders.²⁶ To address periodontal bone defects, guided tissue regeneration (GTR) and guided bone regeneration (GBR) can be employed. To achieve this, barrier membranes are necessary to create a space between the soft connective tissue and the regenerating bone, allowing for the formation of new bone. This process leads to faster differentiation of mesenchymal cells into odontoblasts/osteoblasts, which aids in the regeneration of the bone.⁹ To enhance bone regeneration, the utilization of osteogenic proteins or drugs may sometimes be necessary. The osteogenic properties of cells can be improved by adsorbing drugs or growth factors onto graphene or its derivatives, which leads to an increase in local concentration.¹¹ Dexamethasone (DEX) has been shown to promote osseointegration and improve osteogenic differentiation. Incorporating DEX-GO and DEX-rGO into cell cultures resulted in increased cell proliferation and improved osteogenic differentiation. Graphene has demonstrated the ability to support the attachment and proliferation of various cell types without any observed cytotoxicity. Additionally, graphene has been shown to facilitate rapid differentiation of osteoblastic cells and enhance mineralization.²⁶

Implant

It has been demonstrated that the application of GO coatings can notably enhance the attachment, expansion, propagation, and bone-forming differentiation of mesenchymal stem cells derived from bone marrow. Additionally, GO coatings have been found to promote bone-implant osseointegration.¹⁰ New bone mass and fewer gaps between implants and bone tissue were found around the implants with the GO coating group than in the control group, as shown by van Gieson (V-G) staining of hard tissue sections. Consistent with this, the short sequential fluorescence double-labeling method showed that after 2 weeks almost no alizarin red staining at the sandblasting and acid etching (SLA) implant periphery was observed, whereas the SLA/GO group had significant alizarin staining (after two weeks) and higher fluorescence intensity (after four weeks), the role of GO coating in improving bone deposition around implants is recommended (Figure 3).¹⁴ These effects are also enhanced by GO coating modification in different ways, such as with dexamethasone DEX–GO–Ti and sandblasted and acid-etched Ti discs with GO coating.⁵ Ti implants modified with graphene nanocoating (GN) can maintain their quality and electrochemical structural integrity under biologically relevant stresses.¹⁵ Such as microbial-rich environments and inflammatory macrophages. Specifically, the Ti implant surfaces coated with GN exhibit higher polarization resistance and lower corrosion rates after being exposed to Streptococcus mutans bacteria supplemented with sucrose for a period of eight days GO coatings are beneficial for peri-implant bone formation and stabilization.^18,19 The rGO coating also showed the potential to promote osteoblast differentiation; however, the pro-osteogenic effect of the rGO coating needs further investigation.¹⁷

Teeth Whitening

The teeth whitening process often involves the use of hydrogen peroxide (H₂O₂), which can lead to side effects such as tooth sensitivity and irritation of the gums. However, the rGO nanocomposite has been found to be more effective in teeth whitening than H₂O₂, and can remove stains caused by dyes, coffee, tea, Paan, and betel nuts. This is because rGO nanocomposites act as a catalyst, promoting a faster bleaching process by increasing the reaction between the staining molecules and H₂O₂. ²¹ Therefore, graphene-based materials have the potential to be a beneficial catalyst for teeth whitening when used at the appropriate concentrations and types.

Discussion

Graphene is the thinnest yet strongest material, which is chemically inert and insoluble in oral fluids. It has high deformation resistance and stress limit, thus avoiding the formation of cracks and fractures. A high impact resistance is useful for removable prostheses. The hardness of the material was higher then that of acrylic resins. Graphene and graphene derivatives improve the mechanical prospects of dental materials and, also show good biocompatibility; it may be an ideal material for caries filling.⁶ GO can inhibit the growth of oral pathogens like S. mutans and P. gingivalis, which is helpful in treating caries and periodontal diseases, as well as the success of implantation.¹⁹ The application of nanotechnology in dentistry by creating biological use graphene polymers for milling in CAD/CAM technology.²⁷ A graphene-based polymer disc (G-CAM disc) is a dental material designed to create permanent and rigid structures that improve the dental sector's mechanical, physicochemical, as well as biological properties. G-CAM discs provide better esthetic results compared to zirconia crowns.¹² Dental prostheses may have greater strength, structural flexibility and stability, lighter in weight, which makes them much more ductile.²⁵ Graphene is an electrical and thermal insulator, permitted for absorption, load-bearing of masticatory forces and avoiding bimetallism while still remaining biocompatible.²³ Graphene, a type of nano-reinforced material, has been developed for use in permanent dental structures and prostheses. This material is utilized in various chromatic crowns to achieve a natural aesthetic appearance while also addressing the mechanical, physicochemical, and biological limitations of other commonly used dental materials.²⁴ GO with N-vinyl caprolactam (GOPVCL) can use as the carrier for drugs, anticancer drug composite with graphene may be placed in the tumor bed region after surgical tumor resection to reduce the recurrence of cancer.¹³ Graphene based biosensors are also used for the detecting the small biomolecules (dopamine and glucose), proteins and DNA. Cancer stem cues (CSC) or tumor-stimulating cells exhibit resistance to conventional therapeutic approaches and therefore pose a challenge for cancer treatment.

Conclusion

The utilization of graphene in reconstructive dentistry has been a significant advancement. Due to its 2D structure and exceptional characteristics, graphene has demonstrated its potential in prosthodontics and implant dentistry. The incorporation of graphene-based nanomaterials can enhance the chemical, physical, and mechanical properties of biomaterials, thus offering promising options for innovative therapeutic approaches in dentistry. This paper reviews recent research progress on the potential applications of GFNs in various dental fields, focusing on their antibacterial effects and toxicity on cells. Additionally, the development of GO represents a promising material that can potentially revolutionize both dental and medical practices.

Conflict of Interest

The authors declare no conflicts of interest related to this study.

Financial Disclosure

The authors have no financial relationships or interests to disclose.