Graphene for the development of the next-generation of biocomposites for dental and medical applications

Abstract

Objective

Graphene and its derivatives, graphene oxide (GO) and reduced graphene oxide (rGO), are 2D carbon-based materials with remarkable physical, chemical and biological properties. Graphene sheets have high specific surface area and mechanical strength. Moreover, they have been shown to influence the differentiation of stem cells and to improve properties of biomaterials.

Methods

Here, we present the recent achievements on the use of graphene and its derivatives to improve properties and enhance bioactivity of biomaterials. We also discuss the biosafety constraints to be solved to translate these carbonaceous materials to the clinic.

Results

Graphene and its derivatives can be functionalized and further modified with several bioactive molecules. They can be combined with several biomaterials used in regenerative and reconstructive dentistry and medicine. The resultant graphene-modified composites often present improved physico-mechanical properties and enhanced bioactivity. Moreover, graphene-modified composites are promising candidates to deliver growth factors, drugs and others bioactive compounds.

Significance

Graphene can improve the physical, chemical and mechanical properties of biomaterials. As it can be functionalized and combined with several biomolecules, graphene holds enormous potential to be used as drug carriers or substrates and scaffolds for cell-based tissue engineering strategies.

Introduction

The combination of two or more materials with different compositions, morphologies and properties can result in composites with tailored physical and chemical characteristics, and increased mechanical properties or bioactivity. Due to the enhanced capabilities, composites are widely used in dentistry and other biomedical areas as restorative materials, drug carriers, prosthetic parts and others .

Although composite materials can present several advantages that single-component materials fail to express, they may also present aspects that require further improvements. For instance, thermoplastic resin composites can be less toxic than the thermosetting ones but are prone to slow crack growth . Also, ionomeric polymer–metal composites present large displacements when submitted to low applied voltage but are costly as their manufacturing depends on noble metals such as platinum and silver . Ceramic–polymeric composites can be bioactive but may induce allergic reactions and present low mechanical properties . Even with current advances, the development of new materials and methods to create the next generation of biocomposites with improved capabilities is of high interest.

In this context, emerges graphene emerges ( Fig. 1 ). It is a single atomic sheet of conjugated sp 2 carbon atoms arranged in a honeycomb pattern with extremely high mechanical strength and modulus of elasticity. Moreover, graphene has unparalleled electronic properties and offers a large surface area that can be chemically functionalized . Graphene has two derivatives, namely graphene oxide (GO) and reduced graphene oxide (rGO). GO can be prepared by oxidation of graphite. It presents several functional groups (e.g., hydroxyl, carboxyl and epoxy groups) that can be used to combine GO to several biomolecules and materials . As such, GO is an interesting alternative to improve the mechanical properties and the bioactivity of biomaterials, or as carriers for biomolecules and drugs. The second derivative, rGO, can be produced by removing the oxygen-containing groups of GO with the recovery of a conjugated structure . Although this process results in a material that resembles pristine graphene, oxygen-containing groups and defects in different proportions are found on the rGO surface .

Fig. 1
Key milestones on graphene development.

Pristine graphene can be obtained via several routes (e.g. micro-mechanical exfoliation of graphite, chemical vapor deposition (CVD), epitaxial growth on SiC and others). The graphene produced by these methods presents an almost perfect hexagonal structure with outstanding physical, chemical and mechanical properties, and can be transferred to several substrates . Alternatively, GO and rGO can be produced via cost-effective chemical methods using graphite as raw material . They can be dispersed in stable aqueous solutions to assemble macroscopic structures at large-scale . Nonetheless, their deposition and positioning in pre-defined geometries are very challenging. This is particularly important for the fabrication of devices that require assembling materials with precision in micro- or nano-sized architectures .

The properties of graphene-related materials and their abilities to be functionalized and combined with biomolecules and materials offer several opportunities to design biocomposites with tailored properties. Thus, the objective of this paper is to present the potential of graphene to produce polymer-, ceramic- and metal-based composites with enhanced mechanical properties and enriched bioactivity for several dental and biomedical applications ( Fig. 2 ).

Fig. 2
Potential improvements provided by graphene in biomaterials and key areas to be developed to translate the biocomposites to clinical reality.

Graphene and bioceramics: opportunities for bone regeneration and tissue engineering

Bone tissue regeneration and mineralization are major challenges in the reconstruction of congenital defects, tumor resections and fractures. The spontaneous bone regeneration is often hindered by the volume of bone loss, infections, metabolic disorders or impaired blood supply . One of the most common strategies to increase bone volume is based on the use of grafts. Approximately 2.2 million bone grafting procedures are performed yearly worldwide representing a market of about $2.5 billion . Autologous bone grafts are considered the “gold standard” for bone regenerative treatment but their harvesting require additional surgical procedures that can result in donor-site morbidity, pain and increase treatment cost . Xenografts can overcome some of these disadvantages but they lack viable cells and present high batch-to-batch variability. Moreover, there are risks of immunogenicity and infection transmission .

Alternatively, inert or bioactive ceramic-based synthetic bone substitutes are used in the clinical practice. Bioceramics can be inert (e.g., alumina and zirconia-based ceramics) or bioactive (e.g., hydroxyapatite and other calcium phosphates). The latter category usually present high tissue compatibility and osteoconductivity that can favor the physiological processes involved in the formation of calcified matrix. Typically, bioceramics stimulate the differentiation of stem cells or osteoprogenitor cells into osteoblastic-like cells, resulting in calcification . Despite these advantages, they can be inherently brittle, present slow resorption rates and are difficult to shape . Hence, the development of strategies that can overcome some of these limitations is of great interest. Notably, graphene and its derivatives can be combined with bioceramics resulting in composites with enhanced mechanical properties and improved osteogenic potential in vitro and in vivo.

Hydroxyapatite (HAp) particles have a great potential to induce cell differentiation into the osteolineage . HAp has been combined with graphene for scaffolds and coatings with enhanced capabilities. For instance, the addition of a third component (e.g., chitosan, gelatin or polyethylene glycol) to the HAp/GO derives nanocomposites that can release significantly higher quantities of Ca and P ions compared to pure HAp particles or nanorods . The higher release of these ions may be related to the lower crystallinity of the modified material that increases the rate of dissolution of the nanocomposite . Several improvements in physical and mechanical properties have been observed from the combination of graphene-related materials to HAp. For example, the addition of 2 and 5 wt% of GO to a HAp coating increased the coating adhesion strength to titanium from 1.5 (control) to 2.7 and 3.3 MPa, respectively. Moreover, the GO-modified coating presented higher corrosion resistance as compared to the HAp alone . It was possible to increase HAp’s elastic modulus by 47% and the fracture toughness by more than 200% when combined with 1 wt% rGO . Also, the microhardness of the HAp increases from 322 to 425 HV with the presence of 1 wt% rGO. Also, the addition of 1.5 wt% increases the elastic modulus from 87 to 123 GPa and fracture toughness from 0.8 to 1.5 MPa m 1/2 . GO nanoflakes incorporated in gelatin/HAp scaffolds presented higher yield and compressive strengths comparing to the original gelatin/HAp . The addition of 1 wt% of graphene nanosheets (GNS) to HAp increased the fracture toughness from 0.5 to 1.0 MPa m 1/2 and hardness from 5.5 to 7.2 GPa .

Indeed, HAp is not the only bioceramic that can be improved by graphene-related materials. Bioactive glasses are reactive glass–ceramic materials that present good biodegradability and bone-bonding ability. The incorporation of 0.5 wt% graphene to 58S bioglass via selective laser sintering increase the compressive strength from 23.6 to 48.7 MPa and the fracture toughness from 1.4 to 1.9 MPa m 1/2 . Notably, the presence of rGO in HAp and bioglass influences their properties in a concentration-dependent manner. The addition of 0.5 and 1 wt% rGO as a reinforcement particle to 45S5 Bioglass increases the fracture toughness from ∼0.5 (control) to 0.8 MPa m 1/2 and 1.2 MPa m 1/2 , respectively .

The enhancements of mechanical properties of bioceramics by the controlled addition of graphene family materials are likely to be caused by three-dimensional crack deflection, bridging and sheet pull-out mechanisms . The 2D sheet-like structure of graphene allows a large contact area, and thus possibly greater bond strength, between the graphene and the ceramic grains, reducing crack propagation along grain boundaries. Despite the different chemical properties of graphene, GO and rGO, successful dispersion of each of these graphene materials in ceramics has been demonstrated. Importantly, graphene is able to withstand harsh processing conditions such as high temperature (e.g. up to 1150 °C) and pressure, which may be used during formation of ceramic composites . It should be noted that high temperatures lead to the in situ reduction of GO to rGO . Graphene-based materials also influence the crystal formation of bioceramics. The presence of 1 wt% graphene nanosheets (GNS) in HAp-based composites induced the formation of uniform apatite layers that are thicker than those observed for HAp alone. Interestingly, GNS changed the spatial distribution of the crystals, which grew near or inside the pores in the pure Hap, while crystals permeated the whole surface of the GNS/HAp composites . rGO sheets were able to act as a nucleation surfaces for HA crystal growth from solution, resulting in an intimate contact between the graphene and the HA through van der Waals bonding rather than chemical reaction .

Graphene-modified bioceramics often present enhanced bioactivity. Mesenchymal stem cells (MSCs) cultured in a colloidal dispersion of rGO-coated HAp presented higher alkaline phosphatase (ALP) activity and calcium nodule deposition after 21 days comparing to those cultured with HAp or rGO alone. Moreover, the MSCs treated with the rGO-coated HAp presented high osteopontin (OPN) and osteocalcin (OCN) protein expression . As the latter protein is commonly expressed in late stages of osteoblastic differentiation , it may be feasible that the synergy between rGO and HAp promotes the osteogenic differentiation of these cells . Moreover, MSCs seeded in gelatin/HAp scaffolds presented round morphology while those in the GO-modified version spread and attain a cell sheet-like appearance after 24 h. The GO-modified scaffold induced higher ALP activity after seven days and higher OPN protein expression after 21 days compared to the control .

Other osteoconductive bioceramics such as β-tri-calcium-phosphate (β-TCP) and calcium phosphate (CaP) can also be blended with graphene to further improve their bioactivity in vitro. The combination of GO flakes with β-TCP scaffolds increased the ALP activity and the expression of osteogenic-related genes of bone marrow MSCs. Moreover, the GO-modified scaffold increased the expression of several proteins involved in the canonical Wnt signaling pathway (e.g. WNT3A, LPP5, AXIN2 and CTNNB) suggesting that this pathway may be activated during the enhanced differentiation . GO/CaP nanocomposites increased the protein expression of ALP and OCN and calcification of MSCs compared to cells treated with GO or CaP alone .

Most importantly, the enhancements in osteoblastic differentiation provided by graphene-related materials to bioceramics are not only observed in vitro but also in vivo. It has been shown that critical-sized calvarial defects created in rabbits that were treated with a GO-modified β-TCP scaffold presented higher new bone formation compared to the defects filled with the unmodified β-TCP scaffold. In fact, after eight weeks of implantation, the bone volume/total volume ratios were equivalent to 30% for the β-TCP scaffold and 44% for the GO-modified one . Similar improvements were observed with a rGO/HAp graft that presented bone density considerably higher (52%) compared to HAp alone (26%) and untreated control (17%) in the same type of defect after four weeks .

Numerous types of bioceramics are constantly developed aiming for launch onto the market with the promise of promoting bone tissue regeneration and mineralization. Graphene family materials offer new opportunities to improve mechanical properties and enhance the bioactivity of bioceramics, making these composites interesting alternatives for bony applications.

Graphene and bioceramics: opportunities for bone regeneration and tissue engineering

Bone tissue regeneration and mineralization are major challenges in the reconstruction of congenital defects, tumor resections and fractures. The spontaneous bone regeneration is often hindered by the volume of bone loss, infections, metabolic disorders or impaired blood supply . One of the most common strategies to increase bone volume is based on the use of grafts. Approximately 2.2 million bone grafting procedures are performed yearly worldwide representing a market of about $2.5 billion . Autologous bone grafts are considered the “gold standard” for bone regenerative treatment but their harvesting require additional surgical procedures that can result in donor-site morbidity, pain and increase treatment cost . Xenografts can overcome some of these disadvantages but they lack viable cells and present high batch-to-batch variability. Moreover, there are risks of immunogenicity and infection transmission .

Alternatively, inert or bioactive ceramic-based synthetic bone substitutes are used in the clinical practice. Bioceramics can be inert (e.g., alumina and zirconia-based ceramics) or bioactive (e.g., hydroxyapatite and other calcium phosphates). The latter category usually present high tissue compatibility and osteoconductivity that can favor the physiological processes involved in the formation of calcified matrix. Typically, bioceramics stimulate the differentiation of stem cells or osteoprogenitor cells into osteoblastic-like cells, resulting in calcification . Despite these advantages, they can be inherently brittle, present slow resorption rates and are difficult to shape . Hence, the development of strategies that can overcome some of these limitations is of great interest. Notably, graphene and its derivatives can be combined with bioceramics resulting in composites with enhanced mechanical properties and improved osteogenic potential in vitro and in vivo.

Hydroxyapatite (HAp) particles have a great potential to induce cell differentiation into the osteolineage . HAp has been combined with graphene for scaffolds and coatings with enhanced capabilities. For instance, the addition of a third component (e.g., chitosan, gelatin or polyethylene glycol) to the HAp/GO derives nanocomposites that can release significantly higher quantities of Ca and P ions compared to pure HAp particles or nanorods . The higher release of these ions may be related to the lower crystallinity of the modified material that increases the rate of dissolution of the nanocomposite . Several improvements in physical and mechanical properties have been observed from the combination of graphene-related materials to HAp. For example, the addition of 2 and 5 wt% of GO to a HAp coating increased the coating adhesion strength to titanium from 1.5 (control) to 2.7 and 3.3 MPa, respectively. Moreover, the GO-modified coating presented higher corrosion resistance as compared to the HAp alone . It was possible to increase HAp’s elastic modulus by 47% and the fracture toughness by more than 200% when combined with 1 wt% rGO . Also, the microhardness of the HAp increases from 322 to 425 HV with the presence of 1 wt% rGO. Also, the addition of 1.5 wt% increases the elastic modulus from 87 to 123 GPa and fracture toughness from 0.8 to 1.5 MPa m 1/2 . GO nanoflakes incorporated in gelatin/HAp scaffolds presented higher yield and compressive strengths comparing to the original gelatin/HAp . The addition of 1 wt% of graphene nanosheets (GNS) to HAp increased the fracture toughness from 0.5 to 1.0 MPa m 1/2 and hardness from 5.5 to 7.2 GPa .

Indeed, HAp is not the only bioceramic that can be improved by graphene-related materials. Bioactive glasses are reactive glass–ceramic materials that present good biodegradability and bone-bonding ability. The incorporation of 0.5 wt% graphene to 58S bioglass via selective laser sintering increase the compressive strength from 23.6 to 48.7 MPa and the fracture toughness from 1.4 to 1.9 MPa m 1/2 . Notably, the presence of rGO in HAp and bioglass influences their properties in a concentration-dependent manner. The addition of 0.5 and 1 wt% rGO as a reinforcement particle to 45S5 Bioglass increases the fracture toughness from ∼0.5 (control) to 0.8 MPa m 1/2 and 1.2 MPa m 1/2 , respectively .

The enhancements of mechanical properties of bioceramics by the controlled addition of graphene family materials are likely to be caused by three-dimensional crack deflection, bridging and sheet pull-out mechanisms . The 2D sheet-like structure of graphene allows a large contact area, and thus possibly greater bond strength, between the graphene and the ceramic grains, reducing crack propagation along grain boundaries. Despite the different chemical properties of graphene, GO and rGO, successful dispersion of each of these graphene materials in ceramics has been demonstrated. Importantly, graphene is able to withstand harsh processing conditions such as high temperature (e.g. up to 1150 °C) and pressure, which may be used during formation of ceramic composites . It should be noted that high temperatures lead to the in situ reduction of GO to rGO . Graphene-based materials also influence the crystal formation of bioceramics. The presence of 1 wt% graphene nanosheets (GNS) in HAp-based composites induced the formation of uniform apatite layers that are thicker than those observed for HAp alone. Interestingly, GNS changed the spatial distribution of the crystals, which grew near or inside the pores in the pure Hap, while crystals permeated the whole surface of the GNS/HAp composites . rGO sheets were able to act as a nucleation surfaces for HA crystal growth from solution, resulting in an intimate contact between the graphene and the HA through van der Waals bonding rather than chemical reaction .

Graphene-modified bioceramics often present enhanced bioactivity. Mesenchymal stem cells (MSCs) cultured in a colloidal dispersion of rGO-coated HAp presented higher alkaline phosphatase (ALP) activity and calcium nodule deposition after 21 days comparing to those cultured with HAp or rGO alone. Moreover, the MSCs treated with the rGO-coated HAp presented high osteopontin (OPN) and osteocalcin (OCN) protein expression . As the latter protein is commonly expressed in late stages of osteoblastic differentiation , it may be feasible that the synergy between rGO and HAp promotes the osteogenic differentiation of these cells . Moreover, MSCs seeded in gelatin/HAp scaffolds presented round morphology while those in the GO-modified version spread and attain a cell sheet-like appearance after 24 h. The GO-modified scaffold induced higher ALP activity after seven days and higher OPN protein expression after 21 days compared to the control .

Other osteoconductive bioceramics such as β-tri-calcium-phosphate (β-TCP) and calcium phosphate (CaP) can also be blended with graphene to further improve their bioactivity in vitro. The combination of GO flakes with β-TCP scaffolds increased the ALP activity and the expression of osteogenic-related genes of bone marrow MSCs. Moreover, the GO-modified scaffold increased the expression of several proteins involved in the canonical Wnt signaling pathway (e.g. WNT3A, LPP5, AXIN2 and CTNNB) suggesting that this pathway may be activated during the enhanced differentiation . GO/CaP nanocomposites increased the protein expression of ALP and OCN and calcification of MSCs compared to cells treated with GO or CaP alone .

Most importantly, the enhancements in osteoblastic differentiation provided by graphene-related materials to bioceramics are not only observed in vitro but also in vivo. It has been shown that critical-sized calvarial defects created in rabbits that were treated with a GO-modified β-TCP scaffold presented higher new bone formation compared to the defects filled with the unmodified β-TCP scaffold. In fact, after eight weeks of implantation, the bone volume/total volume ratios were equivalent to 30% for the β-TCP scaffold and 44% for the GO-modified one . Similar improvements were observed with a rGO/HAp graft that presented bone density considerably higher (52%) compared to HAp alone (26%) and untreated control (17%) in the same type of defect after four weeks .

Numerous types of bioceramics are constantly developed aiming for launch onto the market with the promise of promoting bone tissue regeneration and mineralization. Graphene family materials offer new opportunities to improve mechanical properties and enhance the bioactivity of bioceramics, making these composites interesting alternatives for bony applications.

Improving mechanical properties and bioactivity of polymer-based composites with graphene

Polymer-based materials are widely used for dental and biomedical applications since they can be processed in high scale, easily shaped, and chemically tuned to attain specific biological properties . Nonetheless, some of the polymeric materials used in reconstructive and regenerative dentistry and medicine are not suitable for load bearing areas, suffer lack of remodeling and may induce inflammatory reactions. Moreover, their degradation may induce an autocatalytic ester breakdown which lowers the pH in the microenvironment, posing difficulties for cell survival and differentiation . To overcome some of the inherent limitations, graphene and its derivatives can be blended with polymers via several routes ( Fig. 3 ) to produce composites with improved capabilities.

Fig. 3
Possible routes for the modifications of biomaterials with graphenes.

Graphene-related materials and polymers can be blended to produce composites with enhanced mechanical properties. Different graphene derivatives can be selected to achieve good dispersion within different polymers, for example GO can be easily processed with water-soluble polymers. As with ceramic composites, the large surface area provided by the 2D sheet-like structure of graphene likely provides enhanced interfacial adhesion between the phases, and facilitates crack deflection and improved fracture toughness. Notably, the enhancements can be observed even with a low filler loading in the polymer matrix. An unfilled epoxy reinforced with 0.125 wt% functionalized GNS presented increases of ∼65% in the fracture toughness and ∼115% in the fracture energy . Similarly, the incorporation of 2 wt% of GO nanosheets to polyvinylidene difluoride (PVDF) increased the tensile strength by 92% and the Young’s modulus by 192% .

The improvements in properties promoted by graphene are also observed in biopolymers. The addition of 5 wt% GO to polycaprolactone (PCL) increased the modulus of elasticity from 344 to 626 MPa due to higher polymer crystallinity . Films of chitosan blended with 6 wt% rGO sheets with nacre-like layered structure presented significant increases in the Young’s modulus (from 2.4 to 6.3 GPa) and tensile strength (from 88 to 206 MPa) compared to pure chitosan . The addition of 3 wt% GO to chitosan scaffolds increased the hardness from 0.3 to 1.1 GPa and the modulus of elasticity from 2.6 to 6.7 GPa . Likewise, the combination of 0.2w/v% GO to carboxymethyl-chitosan increased the hardness from 0.05 to 0.18 GPa and the elastic modulus from 1.0 to 2.8 GPa . Although chitosan is an insulator, the addition of 1 wt% rGO amplified the conductivity of the composite film to 0.33 S/m while the composite film with 6 wt% rGO presented a maximum conductivity of 1.28 S/m .

Apart from the enhancements observed in physical and mechanical properties, the combination of graphene and polymers can improve the bioactivity and promote stem cell differentiation.

For instance, the addition of GO to electrospun polylactic-co-glycolic acid (PLGA) nanofibrous mats increased the adsorption of dexamethasone, an osteogenic inducer, compared to the unmodified mat. This composite increased the gene expression of collagen I, ALP and OCN in MSCs in the presence of dexamethasone. Notably, irrespective of the presence of dexamethasone, cells in the GO/PLGA scaffolds presented significantly higher amount of OCN protein after 28 days than those in the control scaffold . Similarly, PCL scaffolds modified with GO increased the proliferation of MSCs and induced greater mineral deposition compared to the scaffolds modified with rGO and pure PCL . The combination of rGO to poly-dopamine (PDA) results in composites with a tendency to induce nucleation of hydroxyapatite when soaked in simulated body fluid. The rGO/PDA-based substrates also promoted higher adhesion and proliferation of osteoblastic cells as compared to glass. Remarkably, cells on rGO/PDA substrate spread to an area of 30,000 μm 2 while those on glass reached only 8600 μm 2 . Moreover, the pre-osteoblasts cultured on the rGO/PDA substrate presented higher ALP activity suggesting an enhanced osteogenic differentiation compared to the controls .

Among the natural polymers, chitosan is one of the most explored for tissue engineering and other applications (e.g., sutures, implants and wound dressings). This polysaccharide can present antifungal and antibacterial activity besides having analgesic and hemostatic potential. Nonetheless, chitosan per se is not osteoconductive . The addition of rGO to chitosan can improve specific stem cells functions (e.g. attachment, calcium nodule deposition and OCN protein expression) via nanotopographic features . Notably, the negative charge and polarity of GO increase the adsorption of serum albumin protein by the GO-modified chitosan scaffold compared to chitosan alone . Together, these characteristics may play an important role in the improved attachment and proliferation of pre-osteoblasts in the GO-modified chitosan scaffolds . Similarly, bone marrow MSCs seeded in 0.2w/v% GO/carboxymethyl-chitosan scaffolds presented higher gene expression of OCN, OPN, and ALP after seven days. The improved osteogenic potential of the GO-modified composite was confirmed in vivo where it increased the new bone volume to tissue volume ratio (BV/TV) from 11 to 28% comparing to chitosan alone .

Biocomposites made of silk-fibroin combined with both GO or rGO are promising alternatives for the differentiation of periodontal ligament stem cells (PDLSCs) into osteo/cementoblast-like cells. Silk-fibroin films loaded with GO increased the initial adhesion and proliferation of PDLSCs after seven days as compared to fibroin alone . GO can also be used to improve the handling and confer three-dimensional characteristics for scaffolds made of this biopolymer. Although PDLSCs failed to express definitive genetic markers of chondroblastic (SOX9) and osteoblastic (SP7/OSX and BGLAP) differentiation, an increase in the expression of early osteoblast/cementoblasts markers (COL1A1, RUNX2, BMP2 and ALP) after ten days of culture was observed. Notably, cells in the scaffold loaded with rGO presented positive protein expression of CEMP-1 which is expressed by cementoblasts and their progenitors, even without the use of chemical inducers for the same .

Polymers are widely used for drug delivery systems. In this sense, graphene can be combined with these materials to design enhanced carriers for biomolecules, peptides and anticancer agents . The sheet-like structure of graphene provides a large surface area for drug loading. The carbon lattice structure of graphene allows non-covalent pi–pi interactions between the graphene and hydrophobic molecules, enabling, for example, the loading of small molecule cancer drugs or proteins/peptides with hydrophobic residues. Charged molecules can also be loaded onto GO via electrostatic interactions. To improve biocompatibility and cellular uptake of the graphene materials, the functional groups present on graphene oxide can be used to attach stabilizing polymers such as polyethylene glycol. For instance, GO functionalized with polyethylene glycol (PEG) can be an efficient vector for the intracellular delivery of proteins. The GO/PEG can effectively protect bovine serum albumin from enzymatic hydrolysis without compromising the serum functions . GO functionalized with poly N -vinyl caprolactam (GO-PVCL) can be an effective carrier for the anti-cancer drug camptothecin (CPT). The GO-PVCL loaded with CPT induced significant cancer cell death as compared to the controls. In fact, after three days, the KB cell viability decreased to less than 20% for the loaded GO-PVCL whereas approximately 50% of the cells remained viable when incubated with the unloaded version . SN-38 is an active metabolite of irinotecan (CPT-11) that contributes significantly to its activity. When attached to a GO-PEG complex, SN-38 presented stronger cancer cell killing potential compared to CPT-11 when used to treat human colon cancer HCT-116 cells in vitro .

As shown by these and other reports, graphene family materials can improve significantly the physicomechanical properties of polymeric composites. Indeed, there are several opportunities for further development and optimization of graphene-modified polymer composites such as the optimizations of reinforcement phase size and concentration, understanding of the interfacial adhesion between graphene and the polymeric matrices, processing methods and others. Nonetheless, one major drawback of these combinations is the dramatic color change of the polymers promoted by the addition of these carbonaceous materials. GO and rGO solutions are dark even at very low concentrations and pristine graphene absorbs a significant fraction of white light (pa = 2.3%) . This may pose a new set of challenges for the use of these materials in restorative and prosthetic materials where optical properties are a concern.

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Nov 22, 2017 | Posted by in Dental Materials | Comments Off on Graphene for the development of the next-generation of biocomposites for dental and medical applications
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