Graphene, as a promising material, holds the potential to significantly enhance the field of dental practices. Incorporating graphene into dental materials imparts enhanced strength and durability, while graphene-based nanocomposites offer the prospect of innovative solutions such as antimicrobial dental implants or scaffolds. Ongoing research into graphene-based dental adhesives and composites also suggests their capacity to improve the quality and reliability of dental restorations. This narrative review aims to provide an up-to-date overview of the application of graphene derivatives in the dental domain, with a particular focus on their application in prosthodontics and periodontics. It is important to acknowledge that further research and development are imperative to fully explore the potential of graphene and ensure its safe use in dental practices. Dental diseases are a worldwide concern due to their high prevalence and incidence . MoreovePeriodontitis is an infectious-inflammatory disease that, as it progresses, leads to the destruction of the tissues that support the tooth on the dental arch, which may result in tooth loss. In addition, periodontitis has been associated with the negative evolution and aggravation of some systemic conditions and diseases, such as diabetes mellitus , cardiovEdentulism represents a complex, impairing condition with profound implications for performing functions such as mastication, swallowing, phonation, and aesthetics . EdentulThus, establishing effective dental treatment as well as identifying appropriate therapeutic methods is a priority. Dental technology constantly evolves, and new materials have been developed that respond favorably to mechanical stress and oral bacterial conditions. In this regard, nanomaterials have been emphasized as biomaterials with superior physical, chemical, and biological properties .Nanotechnology is a prerogative of the 21st century and impacts the medical field. Any material used for medical purposes, especially those that have long-term contact with the human body, must have specific biological and mechanical properties, such as not interfering with the host environment, not allowing the growth of bacteria on its surface, and not initiating a local inflammatory response.Graphene fulfills these characteristics, excelling in antibacterial properties and gaining ground in most medical fields, especially dentistry. The antimicrobial effect of graphene-based materials (GBMs) is one of their most exciting properties. This effect is attributed to their physical interaction mechanism with bacteria, which is likely to prevent the development of antimicrobial resistance (AMR) ,18. UnliOne question arises: What is graphene? Graphene is a carbon-based material, first theorized by PR Wallace in 1947 and obtained by Andre Geim and Konstantin Novoselov in 2004 , for whiChemical modifications have produced graphene derivatives, including graphene oxide (GO) and reduced graphene oxide (rGO). These derivatives are highly versatile and more applicable .2 weighs less than 1 mg), and ecological [Among the properties that make graphene so special are: stability at extremely small dimensions , high level of cohesion, hexagonal configuration, and being the most robust material known so far—stronger than steel (200 times), with the same density as diamond (four layers of graphene would support an elephant) , elasticological .Many applications of this material have been implemented in various fields, starting with electronics , energy production and storage , aviation (improving the structure of aircraft wings), telephony, and computers .Medicine is another field that promises to be transformed by graphene. Because this material is thin, flexible, and resistant to the saline solutions that are part of living tissues, graphene is ideal for designing bionic devices. Unlike metal devices, which last only a few years in the human body, graphene can be used for life. Moreover, because graphene is an electrical conductor, it could be used to transmit electrical impulses to neurons, allowing paralyzed people to regain control of their limbs following an accident that resulted in spinal cord damage . The exaThe main fields in which graphene and its derivatives are applied are presented in Among the medical fields that have explored the potential of graphene and its derivatives is dentistry. Ge et al. and Desante et al. emphasized the existing research void regarding the potential applications of graphene in dentistry, which contrasts with its comprehensive utilization in various other medical domains such as drug delivery, imaging agents, biosensors, and tissue engineering scaffolds ,36 Figu. HoweverResearchers at Princeton University have conducted a noteworthy study where graphene is incorporated onto the tooth surface as a tattoo . As grapOur literature research aimed to provide readers with a “broad view” of the potential and applications of graphene-based materials (GBMs) for the treatment of oral conditions, with a specific focus on periodontal disease and edentulism.A narrative review was conducted aiming to answer the question, “Can graphene and its derivatives contribute to the improvement of periodontal and prosthetic treatment”?An electronic search was conducted in the Web of Science digital database using MeSH terms and unspecific free-text words with Boolean operators. The final search terms were defined after iterative trial and refinement processes. The strategy employed was as follows: “graphene periodontal” OR “graphene dental prosthesis” OR “graphene dental material” OR “graphene dental implant” OR “graphene dental restoration” OR “graphene dental scaffold” OR “graphene dental PMMA”, within the topic field, without imposing any year restrictions. The most recent search was carried out in July 2023, yielding a total of 288 studies. Review articles, book chapters, editorial materials, and studies unrelated to the medical field were excluded, resulting in 168 studies published in English between 2013 and 2023 . Followi2/g) [Graphene oxide (GO) and reduced graphene oxide (rGO) are the leading derivatives of graphene, as shown in 2/g) , and its2/g) . The GO 2/g) . Moreove2/g) . GO also2/g) .Reduced graphene oxide (rGO) is obtained by reducing graphene oxide. This process is ecological, and the resulting product is biocompatible and dispersible . rGO canGraphene quantum dots (GQDs) are produced from graphene oxide. They have strong quantum confinement and photoluminescence properties. These properties make GQDs successful in cell imaging .Nanocomposites that use graphene as a base are created by attaching other active agents to either GO or rGO through covalent or non-covalent bonds . For thiGraphene oxide can bond with silver nanoparticles, forming a stable product that favors a more efficient dispersion, which leads to increased antibacterial properties . It has 3O4), or titanium oxide (TiO2) have also been used. The addition of ZnO also enhanced the antibacterial effect of GO based on the membrane stress caused by sharp edges on microbial cells [In addition to metal ions, oxides such as zinc oxide (ZnO), iron oxide  , polyvinThe antimicrobial mechanisms of graphene derivatives are based on both their chemical and mechanical effects . In termAnother antimicrobial mechanism is based on cellular uptake. Following contact between graphene sheets and bacterial cells, the latter are trapped, isolated from the environment, and without access to nutrients . This efChemically, GO can induce lipid peroxidation in bacteria . This phPorphyromonas gingivalis or Fusobacterium nucleatum, are more susceptible to GO than facultative anaerobes (such as Streptococcus mutans) [There is a widely held belief that graphene oxide (GO) possesses a greater capacity to generate reactive oxygen species (ROS) and oxidize reduced glutathione than reduced graphene oxide (rGO) . However mutans) .It is commonly understood that the effects in question are attributable to a combination of mechanical and chemical processes that occur gradually over time. Oxidative stress can facilitate the damage of bacterial membranes by the sharp edges of graphene derivatives through ATP degradation .Candida albicans, Lactobacillus acidophilus, S. mutans, and Aggregatibacter actinomycetemcomitans of rGO and silver (rGp-NS-Ag) composites with those of silver nanoparticles (AgNP) and rGO nanosheets alone. rGp-NS-Ag generated enhanced antimicrobial effects [P. gingivalis in the percentage of 95.45%, as well as a low rate of bacterial adhesion (4.55%), and showed impacts by data related to microstructures, quantity, cell membrane disruption, bacterial cell apoptosis, and bacterial gene expression [The antibacterial effect of graphene derivatives on periodontopathogenic bacteria was investigated. Peng et al. compared the antimicrobial activities against  effects . Treatmepression .S. mutans, F. nucleatum, and P. gingivalis, was assessed. The approach involved using varying concentrations of nanosheets  to determine their impact on bacterial growth. The results of this study revealed that at a concentration of 40 μg/mL, both P. gingivalis and F. nucleatum exhibited complete inhibition of growth in the presence of GO nanosheets. However, a reduction of S. mutans was observed at a concentration of 80 μg/mL [The antibacterial efficacy of GO nanosheets on three distinct bacterial strains, 80 μg/mL . The mecS. mutans, F. nucleatum, and P. gingivalis) [P. gingivalis at 96 h. Moreover, the authors concluded it was broadly effective against multiple pathogens rather than just one strain. It is plausible that the transfer of electrons from bacterial biofilms to the graphene-reinforced titanium element is the underlying mechanism responsible for its anti-bacterial effect. This transfer has been observed to disrupt the bacterial respiratory chain, ultimately reducing microbial viability [P. gingivalis and F. nucleatum included [Graphene-reinforced titanium (Ti-0.125G) was evaluated against the same pathogens  . The deviability . Qin et included .P. gingivalis, F. nucleatum, and C. albicans). When coated with graphene, the researchers observed that the Ti-6Al-4V alloy exhibited enhanced resistance against oral pathogens compared to the uncoated Ti-6Al-4V alloy. Moreover, the graphene-coated Ti-6Al-4V alloy generated a higher concentration of ROS in the pathogens tested than the uncoated Ti-6Al-4V alloy [Wang et al. investigated the antimicrobial properties of graphene-coated Ti-6Al-4V against oral pathogens . The antibacterial mechanism involved is based on the generation of ROS [Pourhajibagher et al. demonstrated that curcumin-coupled GQDs suppress biofilm formation capacity by 76% for periodontopathogenic bacteria n of ROS . Trusek n of ROS . The maiFavorable osseointegration for ceramic and titanium implants and their alloys is still a major challenge in implant-prosthetic therapy. To increase the success and survival rate of implants while reducing potential complications following their placement, treatment of bioinert implant surfaces with various materials has been attempted, aiming for enhanced osseointegration through antimicrobial activity and functionalization of the tissue-implant interface. This interface is the site of interaction with the surrounding tissues where all the osseointegration processes occur—inflammatory reactions, cell recruitment, adsorption of proteins, or biofilm formation .Therefore, graphene is utilized in implants due to its exceptional attributes, including high biocompatibility, physical interaction with biomolecules such as proteins, enzymes, or peptides , effectiSeveral techniques, such as chemical vapor deposition , plasma GO-coated titanium implants stimulated cell proliferation, increased alkaline phosphatase (ALP) activity levels and gene expression levels of osteogenesis-related markers, and promoted BSP, Runx2, and OCN protein expression . Moreove2 nanotubes resulted in significant improvements in various cellular functions, including proliferation, adhesion, migration, and the expression of genes related to adhesion. These enhancements are critical for achieving successful soft tissue sealing [The findings of Cao et al. indicate that the growth of human gingival fibroblasts on TiO sealing .In their research, Gao and his team employed a sandwich-structured dental implant coating featuring graphene oxide encapsulated within mineralized collagen. This innovative structure demonstrated antibacterial properties and improved adhesion, cytoskeleton organization, and proliferation of human gingival fibroblasts, ultimately leading to superior soft tissue sealing .Enrichment of implant surfaces with GO and bioactive proteins was also attempted. Bone morphogenetic proteins (BMPs) are a class of proteins that can remarkably trigger bone growth. Among them, BMP-2 stands out as a potent factor that facilitates the differentiation of stem cells into bone cells, thereby augmenting the integration of implants by encouraging bone regeneration in the region between the implant and the recipient site . The impA study conducted by Ren et al. investigated the impact of GO and rGO dexamethasone-loaded titanium foils, specifically DEX-GO-Ti and DEX-rGO-Ti, on the proliferation and osteodifferentiation of rat bone mesenchymal stem cells (rBMSCs). The study results showed that DEX-GO-Ti significantly enhanced cell proliferation. At the same time, rBMSCs cultivated on DEX-GO-Ti demonstrated elevated expression levels of calcium, proteins, and mRNA, which are closely associated with osteogenic differentiation .Titanium implant abutment surfaces treated with minocycline hydrochloride (MH)-loaded graphene oxide films were placed in a canine model of peri-implantitis  and comp2) are attractive due to their mechanical, physical, and high chemical and thermal stability, combined with the absence of corrosion or toxicity, leading to decreased peri-implant inflammatory reactions [If the literature abounds in research on improving the surface condition of titanium implants with graphene-based materials, there are fewer studies on the association of these materials with zirconia-based implants . Zirconieactions  and higheactions ,118,119 eactions ,128,129.Two groups of graphene-based 2D nanomaterial (GBN) fillers for ceramic composites can be distinguished depending on the number of graphene sheets. Graphene nanoplatelets (GNP) have more than ten layers and a thickness lower than 100 nm, while multi-layered graphene (MLG) has fewer than ten layers. The latter are divided into two classes: reduced graphene oxide (rGO) and few-layer graphene (FLG), with two to about five layers . GraphenAs for coating materials for zirconia surfaces, few attempts were made. Kou et al. produced functionalized multi-walled carbon nanotubes (fMWCNTs) that improved Saos-2 cell attachment by increasing the surface roughness of coated zirconia-based ceramic surfaces . Further2/GNs) composite with a homogeneous distribution of GNs in the ZrO2 matrix using the plasma spraying technique [Li et al. produced a zirconia/graphene nanosheets  sheets through electrostatic forces, resulting in the collection of zirconia ions on the surface of the GO sheets. The characterization techniques employed to analyze the structure of the obtained materials confirmed that the synthesis route assured the successful bonding of zirconia nanoparticles to graphene oxide sheets. It allowed the efficient production of uniform zirconia/graphene nanopowders, both economically and practically.A homogeneous precursor powder must be obtained to produce zirconia-based graphene-containing composites, which are then compacted and sintered. The processing route of graphene-based ceramic composites is of paramount importance for the mechanical properties of the final material . In 2020O powder . The proLorusso et al. conducted a study aimed at assessing the efficacy of biomaterials derived from polymethylmethacrylate (PMMA) in terms of bone integration, with a specific focus on PMMA infused with graphene (GD-PMMA) . In theiPEEK material has become increasingly prevalent in dentistry due to its diverse applications. These applications encompass oral implant treatments such as oral implants and implant abutments, restorative dentistry procedures such as crowns, fixed and removable dentures, posts and cores, and maxillofacial prosthetics, as well as other oral applications such as orthodontic wires and retainers and scaffolds for cartilage repair . It is fIn recent years, advancements have been made in using materials such as carbon nanotubes (CNTs) and graphene to reinforce PEEK composites. The treatment of the surface of the CF/PEEK composite with concentrated sulfuric acid leads to the creation of a three-dimensional porous network. Notably, an increased CF content results in larger pore sizes within this porous layer. Following treatment with a solution of graphene oxide (GO), the sulfonated material exhibits the development of filamentous GO folds on its surface. It has been observed that the contact angles of all samples increase post-sulfonation. However, the GO functional wrinkles cause a significant reduction in the contact angle of the material, leading to an increase in surface hydrophilicity .biomediGraphene oxide is also used to make barrier membranes and scaffolds for periodontal tissue regeneration. During bone regeneration, a barrier membrane is utilized to prevent the infiltration of epithelial cells into the neo-formation site. This promotes optimal healing and ensures the development of new bone tissue. Moreover, such a membrane must possess several properties, which include biocompatibility, site protection and maintenance, cell occlusion, tissue attachment, and clinical sensitivity . In the S. oralis, Veilonella parvula, F. nucleatum, and P. gingivalis, the GO-Ti membrane did not produce toxic or inflammatory effects. Moreover, the multiplication of human gingival fibroblasts and osteoblastic promotion were observed [A titanium membrane was coated with GO in a study conducted by Radunovic. Besides the antibacterial effect exerted on observed . De Marcobserved .Scaffolds for use in periodontal tissue regeneration that have been investigated were made of materials including collagen , poly signaling pathways, which results in significant stimulation of bone growth in laboratory conditions. Furthermore, the use of these scaffolds has demonstrated a noteworthy ability to facilitate bone regeneration in calvarial defects in live subjects .Scaffolds based on chitosan and GO exhibited high water retention capacity, porosity, and hydrophilic nature . HermeneThe association between graphene derivatives and natural polymers, primarily collagen, has also been investigated. Nishida et al. fabricated a GO-coated collagen sponge scaffold and implanted it into the post-extraction alveolus in canine subjects. This scaffold resulted in a fivefold stimulation of bone neoformation compared to the control group .A bilayer composite was synthesized by incorporating silk fibroin into graphene oxide and reduced graphene oxide. This composite has been observed to exhibit beneficial properties in promoting cell proliferation and inducing osteoblastic and cementoblastic cell differentiation in periodontal ligament stem cells . AdditioMulti-composite structures have been developed to enhance the mechanical and biological characteristics of scaffolds. Wang et al. synthesized a scaffold of GO and a collagen/nanohydroxyapatite nanocomposite. The high porosity of the obtained product exhibited improved hydrophilic and mechanical properties and outstanding proliferation potential .Scaffolds based on hydroxyapatite, chitosan, and graphene oxide promoted cell adhesion and proliferation and improved osteogenesis in vitro tests ,176. TheA research team led by Zhang has successfully developed a method that utilizes water-soluble graphene oxide-copper (GO-Cu) nanocomposites to coat porous calcium phosphate (CaP) scaffolds. This innovative coating has demonstrated the ability to significantly enhance the adhesion and osteogenic differentiation of rat bone marrow-derived stem cells (BMSCs). Moreover, these scaffolds stimulated angiogenesis and osteogenesis when transplanted into rats with calvarial defects . A GO scGraphene-based 3D scaffolds have also been developed and investigated for stem cell growth and differentiation. Crowder et al. employed three-dimensional graphene foams as culture substrates for human mesenchymal stem cells. The cells maintained their viability for one week and strongly expressed the osteogenic markers osteocalcin and osteopontin, indicating their spontaneous osteogenic differentiation without extrinsic growth factors . The stuThe great potential of graphene derivates has allowed their use in various fields of dentistry. For direct or indirect restorations, restorative dentistry employs composites, adhesives, and cement types with aesthetic properties and high hardness. However, they face limitations due to high polymerization shrinkage and poor antibacterial properties. Graphene nanoplates (GNPs) are utilized as nanofillers in porous and prone-to-dissolution materials such as resins, cement, and adhesives to effectively reinforce commonly used dental composites and exert an anticaries effect.Adding graphene nanosheets to two different powders of bioactive calcium silicate cement (Biodentine and Endocem Zr) improved bonding time and hardness. However, Endocem Zr experienced significant impairment in bonding properties when adding GNPs. This indicates that while GNPs enhance the physical-mechanical properties of materials, they may not be suitable for all materials in terms of bonding . IncorpoStaphylococcus aureus and S. mutans while exhibiting a favorable release rate of fluoride ions [A graphene variant, Fluorinated Graphene (FG), has been developed and incorporated into glass ionomer cement. In dentistry, FG has emerged as a more desirable option than conventional gray GNPs owing to its visually appealing bright white color, which renders it an excellent choice for aesthetic applications. FG has been used to modify poly(acrylic acid)-based glass ionomer types of cement (GICs), offering advantages in mechanical, tribological, and antibacterial properties. Therefore, the GIC/FG composites exhibit increased Vickers microhardness and compression, flexural strength, and a decreased friction coefficient. This widens the application of glass ionomer cement in restorative dentistry for various procedures, such as restoration of non-carious and carious lesions, class III and class V restorations, and crown cementation. Furthermore, these compounds demonstrate potent antibacterial activity against ide ions .The advantages of GBMs have led to their application in enhancing the properties of adhesive materials . Dental S. mutans cells while simultaneously preserving their bonding properties [GNPs are frequently utilized as fillers in polymer-based dental adhesives owing to their potent antimicrobial and antibiofilm characteristics. These nanocomposites, filled with GNPs, exhibit efficacy in suppressing the activity of operties . Therefooperties . Accordioperties .A research team led by Nizami has successfully developed a composite material known as nHAP/MWCNT-GO that exhibits exceptional properties as a shield for dentin. The composite comprises nanohydroxyapatite, multi-walled carbon nanotubes, and graphene oxide. This material forms a surface film that effectively resists acid and minimizes dentin erosion .S. mutans. Furthermore, the composite demonstrated low cytotoxicity, except at higher concentrations of approximately 0.1 w/v% [In addition, graphene oxide (GO) has been modified by incorporating different nanoparticles, such as calcium fluoride, silver, and tricalcium phosphate, to prevent dentin decalcification. GO combined with silver and silver-calcium fluoride exhibited inhibition of 0.1 w/v% .2 [2, improves surface roughness, and slightly increases the water contact angle [The application of silane primer significantly influences the bonding of zirconia, with the adhesive layer proving to have low mechanical properties . Incorpo2 . Adding ct angle .Dentistry currently utilizes various types of medical materials, each with its own advantages and disadvantages. Regarding prosthodontics, there is a great diversity of materials for indirect restorations, especially those used in CAD/CAM systems . Due to For the past 80 years, polymethylmethacrylate (PMMA) resin has remained a highly favored material within the realm of prosthetic dentistry. This is particularly true for the manufacturing of complete and removable partial dentures. One of the reasons for this popularity is the material’s ease of manufacture, affordable cost, pleasing aesthetic properties, and low modulus of elasticity. Moreover, PMMA resin also boasts easy repair capabilities, making it a versatile choice for dental professionals. Polymethyl methacrylate (PMMA)-based resins find extensive application in provisional restorations due to their low mechanical properties that prevent their use for permanent restorations, considerable polymerization shrinkage, and poor inhibition of biofilms that restrict their use in permanent restorations . EffortsAzevedo et al. have achieved a remarkable result in the realm of maxillary full arch rehabilitation by introducing graphene oxide into PMMA resin, resulting in complete restoration . Recent A study was conducted by Abad-Coronel et al. to compare the fracture resistance of various materials used in temporary restorations. The materials included PMMA, graphene-modified PMMA (GRA), acetal resin (AR), and polysulfone (PS). The purpose of the study was to evaluate the effectiveness of different materials for temporary restorations and their ability to resist fractures. The materials were employed in the fabrication of a three-unit fixed dental prosthesis (FDP) using a milling process facilitated by a CAD/CAM system. During compression testing, it was observed that PMMA displayed substantially lower values in contrast to other materials, whereas PS exhibited the highest values. Moreover, GRA and AR showed similar values, which were still greater than those of PMMA. These findings suggest that GRA, AR, and PS are feasible options for interim milled restorative materials and can potentially serve as substitutes for PMMA. This study highlights the comparative fracture resistance of various materials utilized in temporary restorations and emphasizes the potential benefits of GRA, AR, and PS in this domain .S. aureus, Escherichia coli, and S. mutans [A study was conducted by Bacali et al. that focused on the incorporation of graphene-silver nanoparticles (Gr-Ag) in PMMA. The study aimed to assess the material’s mechanical properties, hydrophilic abilities, and morphology . Accordi. mutans .Candida albicans after 28 days of culturing, indicating a positive impact on hydrophilicity. These results suggest that incorporating nGO into PMMA may have potential applications in improving antimicrobial and antiadhesive properties for medical devices and implants.The utilization of graphene oxide nanosheets (nGO) by Lee and colleagues has been found to effectively enhance the antimicrobial and adhesive properties of PMMA resin . The finAdding less than 1% graphene nanoparticles to the component of PMMA improves the physical characteristics and confers antimicrobial activity . The conNumerous studies have investigated the intrinsic antimicrobial properties of graphene . These pAccording to previous research, the incorporation of graphene within PMMA did not yield a noteworthy effect on the adhesion of microorganisms. This is attributed to the intricate mechanics of microbial adhesion, which are subject to the topographical features and roughness of the material surface and the very low concentration of graphene present in the material .C. albicans growth displayed a proportional relationship with the GNPs content. The alteration did not trigger a toxic reaction, as its biocompatibility remained within the prescribed range for biomedical devices [Research has shown that the incorporation of graphene nanofibers into PMMA resin can significantly improve its mechanical and antimicrobial properties, making it a promising material for CAD/CAM applications. While further research is necessary to fully assess its potential, the findings from previous studies are highly encouraging. The use of graphene nano-reinforced biopolymer in G-CAM discs, designed explicitly for permanent dental structures, offers various benefits. These discs are available in different chromatic crowns, providing a natural aesthetic appearance. Moreover, they address the mechanical, physicochemical, and biological shortcomings associated with other materials currently used in the dental industry. The biopolymer discs nanoreinforced with G-CAM graphene  offer numerous properties for dental structures and meet the requirements to be considered a good material for prosthetic works utilizing CAD/CAM technology . Aati et devices .Despite the increasing research on the antimicrobial properties of graphene-based materials (GBMs), there remain uncertainties regarding the mechanisms underlying their behavior and short-term and long-term effects. GBMs exhibit antibacterial activity independent of antimicrobial resistance (AMR) and do not appear to induce long-term secondary resistance. This unique characteristic makes GBMs suitable for various antimicrobial applications; however, their potential toxicity to the environment and human health needs to be thoroughly understood . ConsideAs a catalyst in oxidative environments, graphene can penetrate cell membranes through its jagged edges and disrupt normal cellular functions ,61,62,69Dziewięcka et al. investigated the cytotoxicity of various graphene oxide nanoparticles based on their structure. They systematically produced and analyzed the particles regarding cell viability, oxidative stress, apoptosis stages, and DNA damage. Biomarkers were correlated with various physicochemical parameters of graphene oxide . The autThe stomatognathic system is a highly intricate and sophisticated physiological mechanism that remains in a perpetual state of flux due to countless environmental, supra-, and sub-systemic factors. Its primary function is to maintain a delicate equilibrium between a host of risk and protective factors. Therefore, it is imperative to precisely identify and quantify any factor that disrupts this equilibrium to determine the most efficacious treatment approach. However, the oral cavity is replete with numerous variables that pose a significant challenge to accurate measurement and prediction .The efficacy of dental treatments is contingent upon the biological and biomechanical responses of restorations, which are influenced by a plethora of factors. Within the dental industry, there exists a persistent demand to extend the longevity of dental restorations, driven by patients, public practitioners, and administrative bodies in the public health sector. Despite significant advancements in biomaterials and restorative techniques, absolute therapeutic success cannot be guaranteed. Nevertheless, there are ongoing initiatives aimed at enhancing existing biomaterials and developing novel ones that surpass current standards .Contemporary dental materials have undergone extensive development through advanced research conducted in diverse fields such as materials science, chemistry, physics, and engineering. For example, dental composites, which are used for aesthetically pleasing fillings and restorations, were developed based on composite materials that were initially employed in the aerospace and automotive industries. Furthermore, titanium, which is widely acclaimed for its exceptional properties such as its resistance to corrosion and biocompatibility, has found extensive use in dentistry thanks to research conducted in the aerospace industry. Moreover, restorative materials used in prosthodontics and CAD/CAM technology are the outcome of research conducted in the fields of engineering and IT. Additionally, groundbreaking research in biomaterial science has led to the development of bioactive materials that can facilitate dentin remineralization. The integration of technologies and materials from other fields has enabled the field of dentistry to make significant progress and offer more efficient, durable, and aesthetically pleasing dental treatments.The remarkable antimicrobial, chemical, physical, and mechanical attributes of GBMs justify the large interest in their application in the biomedical and dental fields , an inteNumerous factors, namely concentration, size, shape, and surface chemistry, exert a significant influence on the properties of graphene derivatives. It is noteworthy that functionalized graphene oxide and reduced graphene oxide exhibit the most robust antibacterial properties among graphene derivatives . FurtherTitanium- and zirconia-based implants are widely regarded as the optimal choice for dental root replacement due to their exceptional biocompatibility, impressive corrosion resistance, and exceptional long-term performance. However, it is worth noting that titanium does have a relatively low shear strength , and zirIt has been found that graphene and its derivatives positively impact the biocompatibility of materials and promote cell adhesion to the substrate. In comparison to the Gelatin-alginate scaffold, the Gelatin-alginate/Graphene oxide scaffold has exhibited superior compressive strength, enhanced cell attachment and proliferation, amplified expression of osteoblast transcription factors, and elevated activity of alkaline phosphatase . The incResearch has shown that a scaffold made from a combination of 3D-printed poly(ε-caprolactone) (PCL) and graphene exhibits improved protein adsorption, cell attachment, and dispersion, as well as increased cell viability and connective and mineralized tissue formation in both laboratory and animal testing. Furthermore, the levels of proinflammatory molecules TNFα- and IL-1β were observed to decrease . In compAnother study discovered that the inclusion of GO within collagen 3D sponges resulted in a noticeable enhancement of osteoblastic differentiation in vitro and an accelerated rate of new bone formation in vivo . TherefoLiterature data have demonstrated that GO can have a low cytotoxic effect, resulting in reduced cell viability . It is nIn prosthodontics, the conventional technology used for manufacturing resin-based restorations negatively affects the materials’ sustainability and their physical, chemical, and mechanical properties. This is primarily due to factors such as resin shrinkage, residual monomer, and porosity. To address and mitigate these shortcomings, 3D technologies have been adopted in conjunction with the incorporation of graphene additives.Nevertheless, the utilization of graphene derivatives poses certain challenges, including toxicity and a paucity of comprehensive knowledge concerning their biological characteristics and pathways. These challenges demand further in-depth examination.Currently, there is a limited amount of research available on the long-term effects of graphene derivatives, which has made their potential toxicity a primary concern. This lack of data has had a significant impact on the widespread use of these biomaterials in clinical settings, and as such, it is crucial to prioritize human safety when considering the use of these materials. To achieve the best possible clinical outcomes, it is necessary to develop solutions to the potential challenges posed by graphene derivatives, including their toxicity and biodegradability. This can be accomplished by developing standardized parameters for their use, as the toxicity and biological features of these materials are inherently linked to their physicochemical properties. Additionally, it is important to note that the effects of graphene derivatives are highly dependent on the dosage and time of exposure, which can significantly impact the potential for detrimental impact on cells through ROS scavenging or oxidative stress.Our research employed a narrative review approach, a method that, besides its scientific value, is also acknowledged for its inherent limitations within the scientific community. The selection criteria for our study have been thoughtfully established by our team, drawing upon our collective experience. Nevertheless, we acknowledge that this method may be prone to subjectivity, and therefore, we have implemented measures to ensure that only the most reliable sources are utilized. Specifically, we have meticulously curated articles from the Web of Science database. By doing so, we have taken the necessary steps to guarantee the quality of the sources used in our study.A comprehensive understanding of the potential use of graphene derivatives within the fields of periodontology and dental prosthodontics was provided. Graphene derivatives have been found to exhibit antimicrobial properties through a combination of mechanical and chemical mechanisms, including cellular uptake, the generation of reactive oxygen species, and sharp-edge-mediated actions. Incorporating derivatives of graphene into coatings for titanium and zirconia-based implants, as well as scaffolds for tissue engineering, has shown promising results in terms of biocompatibility and the formation of new tissue. The physical-mechanical properties of direct and indirect restorations were notably enhanced through the incorporation of various graphene types and concentrations. It has been observed that GO may potentially have a cytotoxic effect that could lead to reduced cell viability. It is important to note, however, that the response of cells to GO is influenced by the specific type of graphene derivative and the concentration utilized in the material.While we cannot definitively confirm whether graphene is currently viable for successful periodontal and dental prosthetic treatments due to the limitations of the investigated materials, our research highlights potential areas for further exploration. Extensive and rigorous research endeavors are imperative in the domains of implantology and tissue engineering to determine the safety and durability of employing graphene derivatives as a viable course of treatment. We maintain the conviction that the unwavering dedication and persistent efforts of researchers hold the potential to pave the way for the development of reliable, efficacious, and tailored therapeutic interventions, ultimately leading to optimal therapeutic outcomes.


Paraffin waxes are a promising material for heat storage with high energy density. Their low thermal conductivity, which limits the speed of charging and discharging in heat buffers, was previously shown to be improved by adding graphene nanofillers. In the present study, using molecular dynamics simulations, the segregation by molecular weight of polydisperse paraffin near graphene flakes is investigated. In liquid bidisperse paraffin composed of decane and triacontane, an aligned layer containing mainly triacontane was observed next to the graphene. Upon slow cooling, the wax crystallised into distinct layers parallel to the graphene sheet, with much stronger segregation by molecular weight than in the crystallised bidisperse wax without graphene. For polydisperse wax, the segregation effect was much less pronounced. The molten paraffin had a somewhat higher concentration of the longest chains in the first layers next to the graphene, but during crystallisation, the molecular weight segregation was only slightly increased. Measurements of crystallinity using an alternative version of the method developed by Yamamoto showed that the layers of wax were highly aligned parallel to the graphene, both in the solid state with all wax crystallised and in the liquid state with one layer of aligned wax above and below the graphene. Thermal conductivity was increased in planes parallel to the graphene flakes. The strong segregation of chain lengths in the bidisperse wax resulted in clear differences in thermal conductivity in the segregated regions. The less segregated polydisperse wax showed less variation in thermal conductivity. An important prerequisite for the ongoing energy transition is the storage of energy . This hoOne specific example of an organic PCM material is paraffin wax . BecauseMany previous studies, both experimental ,11 and mCompared to the TC of graphene (2000–4000 W/(m K) ), the obMany studies have been devoted to establishing a link between the crystallinity and thermal conductivity of polymers. For example, Borhani et al.  have stuZeng and Khodadadi  have carIn their theoretical studies, Wu et al.  and HariThe question of the molecular weight segregation of polydisperse polymer samples in the presence of nanofillers is still an open issue. It is well known that longer polymer chains have higher crystallisation temperatures ,23. UponComputational studies on the influence of paraffin–nanofiller interfaces were done by, e.g., Tong et al. . They peParaffin waxes used in practice usually are polydisperse. Knowing more about the interaction of polydisperse paraffin with graphene will provide insights into the behaviour of the composite material during melting–solidification cycles and enable further optimisation for use in heat storage. Using MD modelling, the interactions between paraffin wax and graphene fillers can be studied at the molecular scale, thereby giving information unobtainable by experiments. This is what we try to achieve in the present study.In the current paper, the influence of the graphene nanofiller on the segregation and resulting TC of the paraffin wax has been investigated. Our main goal is to have computational insights into the possible effects of the atomistically resolved nanofiller surfaces on the induced crystallisation, chain-length segregation and thermal conductivity for monodisperse and polydisperse paraffin-based nanocomposites. Segregation is quantified as the number of atoms belonging to molecules of each chain length per layer and the TC is measured by equilibrium MD (EMD), making use of the Green–Kubo formalism ,29, as wThe article is structured as follows. In In this section, we first consider the applied models for the paraffin–graphene composites and discuss measurement techniques afterwards.All simulations in the present study were performed with the fully atomistic Generalised Amber Force Field  (GAFF). us study  for the The paraffin molecules of different lengths needed to be produced separately, using AmberTools20 as described above. By combining the desired number of chains of each length, an initial configuration of the wax was produced that was very structured and had strong molecular weight segregation. To ensure a total loss of these, the paraffin was heated up to 600 K in the NVT ensemble, at which it was kept for 2 ns and then rapidly cooled down to 300 K. After adding the graphene sheet and the wax together, the composite was again heated to 600 K, held at this temperature for 2 ns and then rapidly cooled down to 450 K. This was done using the Berendsen thermostat and velocity rescale barostat at a pressure of 1 atm. Only the length of the box in the z-direction was allowed to change.Timesteps were set to 2 fs and C-H bonds were constrained using the LINCS  algorithGROMACS ,36 was uAs will be seen in Molecular weight segregation was quantified using relative densities. In each layer, the number density of atoms that were part of a chain of a specific length was determined. Dividing this by the average density (over the full simulation box) of the molecular weight under consideration, the relative density was obtained. This gives an indication of how segregated the chains of respective molecular weights are.Crystallinity was measured with the method developed by Yamamoto , altered(2σ)3  with σ tYamamoto . In addieSV [mT [K] the temperature. For ease of reading, only the definition of heat flux valid for two-body interactions is shown in Equation  measurement technique using the Green–Kubo ,29 formaJ→=1V∑ieiN of slabs. By interchanging the velocities of the coldest atom in the central slab—more specifically, slab number N/2 + 1 with N the total number of slabs—and the hottest atom in the first slab (at the edge of the simulation box), a temperature difference is induced. Once a steady state is reached, the heat flowing from the hot central slab to the cold outer slab is equal to the swapped kinetic energy,J [W/mvvm [kg] at each transfer, t [s] the total time of measurement and LLJ the heat flux [W/mAdditionally, the reverse non-equilibrium MD (RNEMD) technique developed by Müller-Plathe  was usedIn our previous publication , the TC Luo et al.  looked iThe effect of the presence of carbon nanofillers such as graphene on the thermal conductivity of monodisperse paraffin wax was studied, e.g., by Babaei et al. ,44. TheyIn Upon further cooling to 250 K, the decane has also crystallised into clear layers, as shown in The composite containing polydisperse wax at 450 K is shown in In In conclusion, a strong segregation was observed in the bidisperse composite. The presence of the graphene sheet induced the formation of much larger regions with a single chain length than was seen in the bidisperse wax without graphene. In the polydisperse composite, some segregation was present in the molten state. However, upon cooling, this did not increase as substantially as for the bidisperse wax. In comparison to the studies by Wu et al.  and HariApart from the segregation observed in bi-/polydisperse paraffin during cooling near a graphene sheet, the formation of crystalline structures is a striking aspect induced by the presence of the graphene sheet. This will be investigated next. Using a slightly altered version of the technique developed by Yamamoto , the cryIn In From previous studies ,45, it iSince, in the crystalline state, almost all molecules are perpendicular to the z-axis, it is expected that the z-component of TC will be reduced while heat transport along the xy-plane will be enhanced. Furthermore, it was shown previously ,45,46,47The most obvious method to measure TC appears to be the EMD technique using the Green–Kubo ,29 formaFurther TC measurements were done with the RNEMD technique developed by Müller-Plathe , as descIn the bidisperse composite, the same effects are observed. In the liquid state, the aligned layers close to the graphene have an increased TC compared to the fully liquid paraffin, which has a very low standard deviation in TC due to isotropy. In the semi-solid state, in which the triacontane has crystallised close to the graphene while the decane, which is concentrated further away, is still in a liquid state, there is almost a factor 2 difference in the TC of these regions. This agrees with expectation since the molecular weight and alignment are known to increase the TC ,22,45,46The polydisperse composite shows smaller differences in TC between the liquid and solid states. The molten paraffin at a large distance from the graphene shows isotropy, indicated by the very small standard deviation. The two layers closest to the graphene, the first of which has a significantly higher concentration of long molecules, as shown in In summary, in the liquid samples, alignment of the paraffin closest to the graphene sheet results in a higher TC compared to the remaining paraffin. The strong molecular weight segregation of the bidisperse wax during crystallisation results in a factor 2 difference in TC comparing the regions containing mostly long and mostly short molecules, respectively. The differences in the polydisperse paraffin were much less pronounced due to the less pronounced differences in composition.Paraffin waxes are a promising phase change material for heat storage, but significant improvement in their thermal conductivity is needed to enable fast charging and discharging. In the present study, we investigate the influence of a graphene nanofiller on the chain length segregation of polydisperse paraffin and the corresponding changes in TC. Making use of fully atomistic molecular dynamics simulations, the molecular weight segregation of paraffin as a consequence of the presence of graphene in the paraffin matrix, and the effect of this segregation on the thermal conductivity of the paraffin, were studied. With the paraffin in a molten state, a distinct layer above and below the graphene in which the paraffin molecules were highly aligned parallel to the graphene sheet was observed.Measurements of relative densities showed that this layer consisted mainly of the longer chains in the bidisperse paraffin. For the polydisperse paraffin, this effect was also observed, but found to be less pronounced, in agreement with the findings by Luo et al.  for paraA slightly modified version of the crystallinity measurement technique developed by Yamamoto , with whThermal conductivity was measured using two techniques. The equilibrium MD technique using Green–Kubo relations provided the qualitative confirmation that TC in the direction perpendicular to the graphene sheet was strongly reduced in the layered paraffin wax. Using the RNEMD technique developed by Müller-Plathe , TC was The layering in the wax implies an additional bottleneck for heat transport from graphene fillers into the paraffin and vice versa, in addition the limitation of interfacial thermal resistance between the two materials. The findings from this study provide a new direction for the optimisation of the TC of paraffin–graphene composites, suggesting to look into the functionalisation of the graphene surface.Additionally, measurement techniques for TC in the direction perpendicular to the planes of strongly layered materials could be further looked into.


Interactions between graphene, with its wide deployment in consumer products, and skin, the body's largest organ and first barrier, are highly relevant with respect to toxicology and dermal delivery. In this work, interaction of polyglycerol-functionalized graphene sheets, with 200 nm average lateral size and different surface charges, and human skin was studied and their potential as topical delivery systems were investigated. While neutral graphene sheets showed no significant skin interaction, their positively and negatively charged counterparts interacted with the skin, remaining in the stratum corneum. This efficient skin interaction bears a warning but also suggests a new topical drug delivery strategy based on the sheets' high loading capacity and photothermal property. Therefore, the immunosuppressive drug tacrolimus was loaded onto positively and negatively charged graphene sheets, and its release measured with and without laser irradiation using liquid chromatography tandem-mass spectrometry. Laser irradiation accelerated the release of tacrolimus, due to the photothermal property of graphene sheets. In addition, graphene sheets with positive and negative surface charges were loaded with Nile red, and their ability to deliver this cargo through the skin was investigated. Graphene sheets with positive surface charge were more efficient than the negatively charged ones in enhancing Nile red penetration into the skin. Positively and negatively charged graphene sheets interacted with human skin and enhanced penetration of Nile red-loaded into the epidermal and dermal layers of the skin. Moreover, graphene's cargo was released more efficiently into the skin layers after laser exposure. It has also been shown that passivation of graphene oxide by polyethylene glycol stimulates potent cytokine responses in peritoneal macrophages.27 In spite of such negative results and high toxicity, other reports showed no significant toxicity for polyethylene glycol-functionalized graphene sheets, with efficient renal and fecal excretion. Such contradictory results may be due to differences in physiochemical properties of the studied graphene sheets, including size, functionality and surface charge.28 Skin, as the largest and first body's organ is at high risk upon exposing to graphene derivatives. However, our knowledge regarding interactions between skin and graphene derivatives mostly is limited to in vitro studies including interactions with skin fibroblasts,29 keratinocytes and human epidermis.30–32 It has been shown that exposing of HaCaT skin keratinocytes to few layers of graphene derivatives for a short time results in reversible toxicity, i.e., these cells were able to recover from the toxic effects. Moreover, it has been demonstrated that graphene derivatives exfoliated by surfactants induce skin irritation, while others do not provoke an adverse effect upon single exposure.33,34 Considering graphene materials for dermal application, it is essential to address their skin sensitization and irritation as a possible adverse outcome. Recently, an in vivo study suggested dermal exposure of graphene oxide (GO) and few-layer graphene (FLG) has no irritation or sensitization effect on skin immune cells.35As the waste products of graphene derivatives are discharged in greater amounts, due to their production in larger scales for a growing range of applications, the health risks of occupational and environmental exposure to these materials grow in importance.36 They have been used for loading therapeutic agents and targeting these cargos to tumor sites.37 Hyperbranched polyglycerol and polyglycerol-based nanomaterials are hydrophilic polyfunctional vectors with low immunogenicity and high potential for future biomedical applications.38,39 Passivation of graphene sheets with polyglycerol has resulted in two-dimensional platforms with unique physicochemical properties and high potential for future biomedical applications.40–44 Interactions of polyglycerol-functionalized graphene sheets with cells, their cellular uptake pathways, and even their journey inside the cells depend strongly on their functionality, size and surface charge.45,46 Considering these factors, polyglycerol-functionalized graphene sheets have been used for various biomedical applications, including pathogen incapacitation and tumor therapy.43,47 Moreover, polyglycerol and similar polymeric nanocarriers have been used as topical drug delivery systems abundantly,39,48,49 but their main disadvantage is the lack of a stimuli-responsive factor to trigger the release their cargo in the target tissue. Hybridization of polyglycerol with graphene results in new systems, which can respond to laser as a triggering factor. In addition, graphene will improve interactions of polyglycerol derivatives with the biosystems, as it has been observed for single cells.45,50On a positive side and in the less-toxic concentration range, polymer-functionalized graphene sheets are interesting candidates for biomedical applications due to their high loading capacity, fast cellular uptake, and photothermal property.Accordingly, polyglycerol-functionalized graphene sheets can be used as new topical drug delivery systems, owing to their high loading capacity for hydrophobic drugs such as tacrolimus (TAC). Acceleration of the rate of release of their cargo in the target tissue decreases their side effects and increase their therapeutic efficiency. Moreover, they can induce heat in the target layer of skin, resulting in photothermal therapy. Due to such properties, polyglycerol-functionalized graphene sheets can be used for the sustainable delivery of topical drugs. They can enhance the bioavailability, stability and skin penetration of drugs, which in turn increase their therapeutic effects.This work uses microscopic techniques to investigate interactions between human skin and polyglycerol-functionalized graphene sheets with 200 nm lateral size and different surface charges . While n51 Hyperbranched polyglycerol (hPG), with Mn ≈ 10 000 g mol−1, was synthesized via one-pot, ring-opening anionic polymerization (ROAP).52 hPG covered TRGO (hPG-Gs), hPG-amine covered TRGO (hPGN-Gs) and hPG-sulfate covered TRGO (hPGS-Gs) with a size of around 200 nm were prepared according to our previously published articles.45,46 IDCC NHS-ester  was bought from IC Discovery GmbH. Cell counting kit-8 (CCK-8) assay, Hoechst 33342 were purchased from Thermo Fisher Scientific. Milli-Q water was used in all experiments. Phosphate-buffered saline (PBS) (10×) pH 7.4 (Thermo Fisher Scientific) was diluted 10 times with Millipore quality water.Thermally reduced graphene oxide (TRGO) was synthesized according to the method in literature.53 by means of an Agilent 1260 Infinity LC system coupled to an Agilent 6490 triple quadrupole-mass spectrometer  interfaced with an electrospray ion source operating in the positive ion mode (ESI+).Atomic Force Microscopy (AFM) was measured with a MultiMode Nanoscope V scanning probe microscopy (SPM) system  in air under ambient conditions. Zeta potential data were obtained in PBS solution by Malvern (UK) NANO ZSPO. For transmission electron microscopy (TEM) a 5 μL droplet of sample solution was placed on a hydrophilized carbon film covered copper grid (400 mesh). The supernatant fluid was removed by blotting with a filter paper and the sample was allowed to dry in air. A standard holder was used to transfer the dried samples into a Talos L120C transmission electron microscope  operated at an acceleration voltage of 120 kV. Micrographs were recorded with a 4k × 4k Ceta 16M camera. The near-infrared (NIR) laser irradiation was performed with a diode infrared laser module (808 nm), Changchun New Industries (China). CCK8 assay was measured with a TECAN (Switzerland) Infinite M200 Pro microplate reader. Confocal laser scanning microscopy (CLSM) was conducted by Leica microscope (Germany) TCS SP8 (63× oil-immersion objective lens). Tacrolimus quantification by stable-isotope dilution liquid chromatography tandem-mass spectrometry (LC-MS/MS) was performed as reported2O): λmax: 500 nm (1 mg mL−1).hPG-Gs  was dissolved in dry DMF (10 mL). IDCC  was added, and the solution was stirred for 48 h at 60 °C. The solution was cooled to room temperature and dialyzed against deionized water for 48 h to obtain the IDCC – . IDCC labeling of hPGN-Gs and hPGS-Gs were performed with the same procedure UV/vis (H1 mg hPG-Gs was dispersed in 10 mL PBS. Then 2 mg TAC (dissolved in 0.5 mL ethanol) was added dropwise into the GH dispersion under stirring at room temperature. The mixture was stirred for 1 h before it was centrifuged at 2000 rpm for 5 min. The supernatant was dialysis in Milli-Q for 24 h to get TAC-loaded hPG-Gs and the precipitate was collected for the measurement of loading capacity. The precipitate was dissolved in 10 mL ethanol. Then the ethanol solution was centrifuged at 5000 rpm for 10 min and 1 mL supernatant was extracted. Subsequently, the solvent was evaporated and the dried TAC was dissolved in acetonitrile for HPLC measurement to determinate the TAC concentration. TAC-loaded hPGN-Gs and TAC-loaded hPGS-Gs could be obtained with the same procedure. The loading capacity of hPG-Gs, hPGN-Gs and hPGS-Gs was determined by the HPLC results.−1) of Nile red in methanol was added to a PBS solution of hPG-Gs, hPGN-Gs and hPGS-Gs dropwise, while mixture was gently stirred . It was stirred for additional 2 h at 25 °C and then methanol was evaporated. Subsequently, hPG-Gs, hPGN-Gs and hPGS-Gs loaded with Nile red were dried at 50 °C for 1 h. The obtained compound was dissolved in MilliQ water and stirred for additional 10 min at room temperature (25 °C). The mixture was centrifuged for 10 min at 3000g and the supernatant was collected and lyophilized. UV/vis (methanol): λmax: 350 nm (0.001 mg mL−1).A 60 μL stock solution  stirred at 500 rpm. After 30 min, 36 μL of the test formulations and cream was administrated onto the skin surface (finite-dose approach) and incubated for 18 h. Furthermore, after 6 h of incubation time hPGN-Gs and hPGS-Gs samples were irradiated with NIR laser  continuously over 30 min for a total exposure time of 2.5 min and samples were remained for another 12 h. Subsequently, the treated skin areas were punched, embedded in tissue freezing medium and stored at a low temperature (−80 °C). To determine Nile red penetration, the skin was cut vertically into 10 μm thick slices using a cryotome. Subsequently, the slices were subjected to normal and fluorescence light .To investigate the interaction of graphene derivatives and topical drug delivery efficiency, IDCC-labelled or nile red-loaded (0.001% w/w) hPG-Gs, hPGN-Gs and hPGS-Gs was studied on excised human skin  and in accordance with the Declaration of Helsinki guidelines. The 55 skin samples were fixed in Karnovsky solution  overnight, washed in 0.1 M cacodylate buffer , and incubated in 1% osmium tetroxide  for 4 h. Samples were dehydrated in an ascending series of ethanol followed by the intermedium propylene oxide . The specimens were subsequently embedded in a mixture of Agar 100 (epoxy resin), DDSA (softener), MNA (hardener) and DMP 30  . Polymerization was done at 45 °C and 55 °C, each for 24 hours. Semi- and ultrathin sections were cut using an Ultramicrotome Reichert Ultracut S . Semi-thin sections (0.5 μm) were stained with modified Richardson solution for 45 seconds on an electric hot plate adjusted to 80 °C. Semithin sections were examined with a light microscope Olympus CX21 . Next ultrathin sections (80 nm) were mounted on nickel grids , contrasted with Uranyless EM stain followed by Reynolds lead citrate 3%  and examined with a transmission electron microscope JEM-1400 plus .After application of the graphene sheets according to our previously reported paper,Ultrathin sections were mounted on Formvar filmed grids and frozen before the transfer into the transmission electron microscope by the use of a Vitrobot™ Mark IV . The Vitrobot was operated at 22 °C and at a relative humidity of 100%. The grids were plunged without further treatment into liquid ethane just above its freezing point and transferred in liquid nitrogen. The grids were “clipped” (= inserted in a rigid clip-ring) and transferred under liquid nitrogen into a Talos Arctica™ TEM (Thermo Fisher Scientific) operated at an accelerating voltage of 200 kV and at a nominal magnification of 4300× or 2600×, respectively. Image series in the tilt range of −64°/64° (2° tilt-increments) were recorded at full 4k resolution resulting in a pixel size of 4.91 nm or 8.01 nm, respectively. The defocus value was set to −20 μm. Image stack alignment and 3D reconstruction were performed in the context of the Inspect 3D software V4.3 (Thermo Fisher Scientific). Stacks of 10 image slices from the reconstructed volume were exported for data presentation.2 at 37 °C. CCK8 assay. HaCat cells (1 × 104 cells per well) were seeded in 96-well plates with 100 μL DMEM and incubated for 24 h before the tests. hPG-Gs, hPGN-Gs and hPGS-Gs in the culture medium were added to the medium-removed 96-well plates with different concentrations and incubated for another 24 h, respectively. After that, the culture medium solutions were removed and the cells were rinsed with PBS twice. 100 μL culture medium with 10 μL CCK8 solution was added to each well. After incubation for the following 2 hours, 75 μL medium was carefully transferred to a new plate to avoid the influence of graphene on final results, and the absorption was measured at wavelength of 450 nm with a microplate reader. Cells without any treatments were regarded as a negative control. Each sample was measured 3 times.All cell experiments were conducted according to German genetic engineering laws and German biosafety guidelines in the laboratory (level 1). Dulbecco Modified Eagle Medium (DMEM) (Gibco) and fetal bovine serum (FBS) were applied for the following experiments. HaCat cells were cultured in DMEM supplemented with 10% (v/v) FBS and 1% penicillin. The cells were incubated in a humidified atmosphere with 5% CO−1), washed twice with PBS, and covered with fresh cell culture medium (DMEM). Confocal images were taken with an inverted confocal laser scanning microscope Leica DMI6000CSB SP8  with a 63×/1.4 HC PL APO CS2 oil immersion objective using the manufacturer-given LAS X software in sequential mode with the following channel settings: transmission Ch , excitation laser line 405 nm, detection of transmitted light (photomultiplier); Ch1 (Hoechst 33342): excitation laser line 405 nm, detection range 410–484 nm (hybrid detector); Ch2: excitation laser line 488 nm, detection range 493–712 nm (hybrid detector).The uptake of IDCC-labeled hPGN-Gs and hPGS-Gs by HaCat cells was analyzed using confocal laser scanning microscopy (CLSM). The cells were propagated as described above. For CLSM, HaCat cells were seeded in eight-well ibidi slides (ibidi treat) in 270 μL of DMEM. After cell attachment for 4 h to 24 h, 30 μL of a postseeding solution containing compound was added, and the cells were further incubated overnight. Before imaging, the cells were stained with Hoechst 33342 (1 μg mL−2) for 5 min every 2 h. The amount of released TAC at different time frames was determined by LC-MS/MS method. To this end, lyophilized samples were resuspended in acetonitrile containing 1 μM stable-isotopically labeled TAC. Samples were then shaken at 200 rpm for 1 h before particles were allowed to sediment for 1 h and supernatants were analyzed. The drug release studies were performed in triplicates.hPGN-Gs and hPGS-Gs with 50 μg TAC content was dispersed separately in PBS , and equally transferred into 2 dialysis tubes (spectra/Por MWCO 2 kD). Then, the tubes were immersed in 2 vials containing 30 mL PBS (pH 7.4). Vials were set up in a thermostatic water bath (37 °C) on a heating rotator. 5 mL solution from PBS medium out of dialysis bag were collected at each 2 h intervals, and meanwhile, fresh PBS was replenished. One of the vials was irradiated with NIR laser  and then equally distributed into 2 tubes. Subsequently, near-infrared (NIR) laser irradiation  was performed to these tubes for 5 min. The temperature of the solutions in tubes were recorded by IR thermal imaging camera .hPGS-Gs and hPGN-Gs were dispersed in 2 mL PBS  at 100 μg mL−1. Afterwards, the uptake of the functionalized graphene sheets, hPGN-Gs and hPGS-Gs, by HaCat cells at different time frames was monitored. According to our previous study, hPG-Gs showed no significant uptake due to the polyglycerol coverage.40–43 While the negatively charged counterparts with sulfate functional groups showed considerable uptake after 24 h  for 3 minutes increased their temperature to 65 °C , a topical therapeutic agent for treating T cell-mediated diseases such as eczema and psoriasis. TEM images of hPGN-Gs and hPGS-Gs after loading with tacrolimus showed sheets with comparable dimensions as before drug loading  for tacrolimus, and they were able to release the drug under short-term NIR laser irradiation. In addition, skin penetration experiments of Nile red-loaded hPGN-Gs and hPGS-Gs confirmed that NIR irradiation increases the release of Nile red inside the skin. In particular, hPGN-Gs enhanced the Nile red's penetration in the viable skin layers more efficiently than hPGS-Gs. Therefore, the potential health risk of graphene should be considered and investigated further, e.g. in in vivo experiments. Outcomes of this work shed a light in the future biomedical applications and toxicity of similar carbon based nanomaterials including fullerene, carbon nanotubes and graphitic materials upon exposure to human skin.This study evaluates possible interactions between of functionalized graphene sheets with lateral size 200 nm and different surface charge – hPGN-Gs (+30 mV), hPG-Gs (0 mV) and hPGS-Gs (−30 mV) – and human skin. As a first step, we evaluated cytotoxicity and cellular uptake of these materials against HaCat cells for 24 h incubation time. The results demonstrate that hPGN-Gs, hPG-Gs and hPGS-Gs do not show significant toxicity up to 30 μg mLex vivo skin studies, data interpretation, writing—original draft preparation, visualization, F. Z.; synthesis, in vitro cell studies, drug loading and release studies Z. T.; LC-MS/MS measurements, data interpretation, visualization, methodology, F. S.; TEM imaging from graphene sheets, data interpretation, visualization, K. L.; TEM imaging from skin samples, data interpretation, visualization, S. K. and C. B.; ex vivo studies, data interpretation, visualization, F. R.; conceptualization, guidance, resources, funding acquisition, B. K.; J. P.; S. H.; A. V. and R. H. All authors have read and agreed to the published version of the manuscript.Conceptualization, methodology, There are no conflicts to declare.NA-005-D3NA00574G-s001


ChatGPT (OpenAI) has gained considerable attention because of its natural and intuitive responses. ChatGPT sometimes writes plausible-sounding but incorrect or nonsensical answers, as stated by OpenAI as a limitation. However, considering that ChatGPT is an interactive AI that has been trained to reduce the output of unethical sentences, the reliability of the training data is high and the usefulness of the output content is promising. Fortunately, in March 2023, a new version of ChatGPT, GPT-4, was released, which, according to internal evaluations, was expected to increase the likelihood of producing factual responses by 40% compared with its predecessor, GPT-3.5. The usefulness of this version of ChatGPT in English is widely appreciated. It is also increasingly being evaluated as a system for obtaining medical information in languages other than English. Although it does not reach a passing score on the national medical examination in Chinese, its accuracy is expected to gradually improve. Evaluation of ChatGPT with Japanese input is limited, although there have been reports on the accuracy of ChatGPT’s answers to clinical questions regarding the Japanese Society of Hypertension guidelines and on the performance of the National Nursing Examination.The objective of this study is to evaluate whether ChatGPT can provide accurate diagnoses and medical knowledge for Japanese input.Questions from the National Medical Licensing Examination (NMLE) in Japan, administered by the Japanese Ministry of Health, Labour and Welfare in 2022, were used. All 400 questions were included. Exclusion criteria were figures and tables that ChatGPT could not recognize; only text questions were extracted. We instructed GPT-3.5 and GPT-4 to input the Japanese questions as they were and to output the correct answers for each question. The output of ChatGPT was verified by 2 general practice physicians. In case of discrepancies, they were checked by another physician to make a final decision. The overall performance was evaluated by calculating the percentage of correct answers output by GPT-3.5 and GPT-4.Of the 400 questions, 292 were analyzed. Questions containing charts, which are not supported by ChatGPT, were excluded. The correct response rate for GPT-4 was 81.5% (237/292), which was significantly higher than the rate for GPT-3.5, 42.8% (125/292). Moreover, GPT-4 surpassed the passing standard (>72%) for the NMLE, indicating its potential as a diagnostic and therapeutic decision aid for physicians.GPT-4 reached the passing standard for the NMLE in Japan, entered in Japanese, although it is limited to written questions. As the accelerated progress in the past few months has shown, the performance of the AI will improve as the large language model continues to learn more, and it may well become a decision support system for medical professionals by providing more accurate information. ChatGPT based on GPT-3.5 was launched by OpenAI in 2022 and has become sensational owing to its capacity to respond to any question using natural language. GPT-3.5 has 175 billion parameters in its language model, while GPT-4, introduced a few months later, did not disclose its number of parameters . The useThe usefulness of ChatGPT in English is widely appreciated . It is aThe objective of this study is to evaluate whether ChatGPT can provide accurate diagnoses and medical knowledge from Japanese input. We input questions from the NMLE into GPT-3.5 and GPT-4 in Japanese and validated the responses. We assumed that the system would output medical information with a high degree of accuracy, even if the input is in Japanese, as its usefulness is increasingly being acknowledged in many fields.Questions from the National Medical Licensing Examination (NMLE) in Japan, administered by the Japanese Ministry of Health, Labour and Welfare (MHLW) in 2022, were used. All 400 questions were included. Figures and tables that ChatGPT could not recognize were excluded, and 292 questions with only text questions were selected. We instructed GPT-3.5 and GPT-4 to input the Japanese questions as they were and to output the correct answers for each question. The output of ChatGPT was verified by 2 general practice physicians. When there were discrepancies, they were checked by another physician to make a final decision. The overall performance was evaluated by calculating the percentage of correct answers output by GPT-3.5 and GPT-4.Because the data studied by GPT-3.5 and GPT-4 were text data available on the internet until September 2021, the target for evaluation was the NMLE held in February 2022, for which the MHLW officially published the questions and answers . There aAs ChatGPT does not allow for the input of images and tables, these questions were excluded (102 questions). In addition, questions that are officially designated as “unscored” by the MHLW, which sponsors the NMLE, were excluded (6 questions). Unscored questions were excessively difficult in terms of the test difficulty level or had errors in their formulation, resulting in situations where the selection of a single answer is impossible for single-choice questions, among other cases. Finally, 292 questions that could be used to accurately assess ChatGPT were included .GPT-3.5 was used on January 30, 2023, and GPT-4 was used on March 24, 2023. ChatGPT is an AI language model based on the GPT architecture, which is a type of neural network designed for natural language processing tasks. It generates responses on the fly based on the likelihood of the next word, given the relationships between words within the neural network learned during training. ChatGPT is specifically designed for conversational interactions. It can engage with users, answer questions, and sustain conversations. By analyzing the preceding text and context, ChatGPT generates responses aimed at mimicking human-like conversations.In the context of ChatGPT, prompts containing target questions are inputted. A new chat was created for each question to prevent the effect of prior input questions . Each quThis study did not involve human or animal participants and ethics approval was not required.In GPT-4, 227 of the 292 questions were answered correctly in 1 attempt (77.7%), 47 were answered incorrectly (16.1%), and 18 (6.2%) of the questions were not completed in the form of answers . Specifically, although 1 answer had to be chosen from a list of options, 2 answers were selected for 8 questions, 3 for 4 questions, 4 for 3 questions, and no answers for 3 questions. Finally, answers to these questions were obtained by adding a “choose one” option to the question. The overall correct response rate was 81.5% (237/292); 88.1% (74/84) for the required questions, 75.4% (89/118) for the comprehensive questions, and 82.2% (74/90) for the specific questions.In GPT-3.5, 102 questions were correctly answered in 1 attempt (34.9%), 143 questions incorrectly (50%), and 47 (16.1%) were not completed in the form of answers . Specifically, regarding the questions where 1 answer was chosen from a list of options, 2 answers were given for 3 questions, 3 for 7 questions, 5 for 3 questions, and no answers for 34 questions. For these questions, we added the option of choosing 1 answer. For the 22 questions that did not receive an answer because there were multiple queries in response to the question text, the queries were inputted separately into the chat box and answers were obtained. The correct response rate was 42.8% (125/292) overall, 50% (44/84) for the required questions, 40.7% (48/118) for the comprehensive questions, and 38.9% (35/90) for the specific questions .In addition to answering the choices, the output included secondary information related to the medical vocabulary in the explanations and question text. These were found in 94 questions in GPT-3.5 and 255 questions in GPT-4. As shown in The primary outcome of this study was the ability to accurately understand medical information by inputting Japanese prompts, and the NMLE was tested as a method of evaluating this ability. This study evaluated whether the selected option was the correct answer. The number of correct answers was calculated and evaluated, first to see if ChatGPT could obtain a score percentage that would pass the examination. GPT-4 was above the passing standard for the NMLE  while GPT-3.5 was below. These results are similar to those of a previous study that tested the performance of ChatGPT on the USMLE . We did We have not been able to evaluate the image and table questions because they are not supported in GPT-3.5 and cannot be inputted in GPT-4 at this time. If all ChatGPT versions could answer the 102 questions containing figures and tables, and the answers were incorrect, it is possible that the passing criteria would not be met. However, many questions that include images and tables use them in addition to clinical information, and it remains possible that the correct answer could have been given based on the question text, even if the images and tables were not discussed. The versions used in this study, namely, GPT-3.5 and GPT-4, were evaluated as of January 30, 2023, and March 24, 2023, respectively. Further updates are expected in the future, and they should be continuously evaluated.GPT-4 reached the passing standard for the NMLE in Japan with prompts entered in Japanese, although it is limited to text-only questions. As the accelerated progress in the past few months has shown, the performance of the AI will improve as the large language model continues to learn more, and it may well become a decision support system for medical professionals by providing more accurate information.


The polyimide polymer was the source material for the fabrication of the LIG. The doping process was performed in situ using the CO2 laser, which works as a rapid thermal treatment to combine graphene and NiO particles. NiO was used to improve the capacitance of graphene by combining an electric double-layer capacitor (EDLC) with the pseudo-capacitance effect. The high-resolution transmission electron microscopy, energy-dispersive X-ray spectroscopy, and Raman spectroscopy showed that the structure of the LIG is multilayered and waved. The HRTEM image proves the distribution of NiO fine particles with sizes of 5–10 nm into the graphene layers. The electrochemical performance of the as-prepared LIG was tested. The effect of the combination of the two materials (oxide and carbon) was investigated at different concentrations. The LIG showed a specific capacitance of 69 Fg−1, which increased up to 174 Fg−1 for the NiO-doped LIG. The stability investigations showed that the electrodes were very stable for more than 1000 cycles. This current study establishes an innovative method to improve the electrochemical properties of LIG.Herein, we have reported a novel strategy for improving the electrochemical performance of laser-induced graphene (LIG) supercapacitors (SCs). The LIG was prepared using a CO It has been suggested that SCs are an alternative solution for single and hybrid applications compared with other storage devices . In addiSCs are categorized into electric double layer capacitors (EDLC)  and pseu2 hybrid orbitals in a hexagonal honeycomb lattice. The combination of these unique physicochemical properties makes graphene-based materials promising candidates for electrochemical energy storage devices [Graphene material has interesting properties due to its high electrical conductivity, high surface area, mechanical strength, and lightweight ,8. There devices ,12,13,142 lasers has been reported [2/g [A method to produce multilayer graphene (laser-induced graphene (LIG)) from polyimide polymer films using COreported ,16. Laseted [2/g ,16. In a2 laser technology. The structure of the LIG was studied using electron microscopy, EDX, and Raman spectrometry. LIG and doped LIG were investigated as supercapacitor electrodes. The performance of the LIG electrodes was significantly improved by NiO doping. An extensive study was carried to analyze the electrochemical properties of the manufactured electrodes. However, one must keep in mind that increasing the capacitance value does not mean only a modification of the intrinsic capacitance of the electric double layer. The higher capacitance of the capacitors may result from combining the pseudo-capacitance and EDLC mechanisms of charge storage. This type of capacitor is often confused with typical redox-based storage. In this work, we present an easy and simple method to improve the storage properties of graphene by merging NiO directly using CO2, corresponding to 2.5 mL of NiO-suspended solution, and 2.0 mg/cm2, corresponding to 5.0 mL of NiO-suspended solution, were wisely dropped on 5.0 cm2 of the fabricated LIG sheet during drying at 60 °C on a hot plate. Afterward, the sheet was again subjected to the laser beam under the same conditions. The steps of the LIG preparation are shown in 2 and 2.0 mg/cm2, three electrodes termed LIG-0, LIG-1, and LIG-2 were prepared, where LIG-0 stands for pristine LIG, LIG-1 stands for NiO-doped LIG with 1.0 mg/cm2 of NiO, and LIG-2 stands for NiO-doped LIG with 2.0 mg/cm2 of NiO.The suspended NiO was prepared based on the prescribed NiO amount using ethanol. NiO nanopowder with a particle size of less than 50 nm was purchased from Sigma Aldrich and was used without further modification. An amount of 10 mg NiO was added to 5 mL of ethanol at a concentration of 2 mg/mL. The suspended solution of NiO was sonicated for 20 min before withdrawing the required amount. The laser system contained 40 W of the maximum power with a head speed of 400 mm/s. Polyimide sheets  with a thickness of 5.0 mil (170 µm and 10 mm × 50 mm) were used as raw materials for LIG. To fabricate the LIG, the laser power was 9.0 W and the head speed was 120 mm/s. Then 1.0 mg/cm−1 were used for measuring the cyclic voltammetry curves. The electrodes were charged and discharged (GCD) at current densities of 1.6 to 3.3 Ag−1.A high-resolution transmission electron microscope  working at 200 kV was used to analyze the products. For TEM measurements, the sample was dropped on a carbon-coated copper grid after the sonication in ethanol. Selected area electron diffraction (SAED) was carried out for the pristine and doped graphene. The Raman shift of the graphene was carried out using LabRAM-HR800 of a He-Cd laser with a wavelength of 633 nm. The supercapacitor measurements were measured using the CorrTest electrochemical workstation. The experiments were carried out in a three-electrode electrochemical cell including a counter electrode of Pt wire, a reference electrode of saturated calomel electrode (Ag/AgCl), and a working active electrode. The aqueous electrolyte was 1.0 M KOH. Within a frequency range of 0.1 Hz to 1.0 MHz, the electrochemical impedance spectrum (EIS) was examined. Various swipe voltages of 5 to 100 mVs2 laser. The lattice image of the LIG with a wide scale shown in For more deep information about the NiO particle size and distribution on the graphene surface, HRTEM images were examined for the NiO-doped graphene sample, as shown in 2g of the sp2 bond in the Brillouin zone center [−1, which could be assigned to disordered graphitic carbon and the presence of sp3 defects [−1 for the LIG. The Raman spectra of the NiO-doped LIG are also shown in −1 [−1 and longitudinal optical (LO) at 530 cm−1) and two phonons  excitations. For pristine LIG, the intensity ratios of the D/G and 2D/G bands are important parameters, which give more details about the nature of LIG, where ID/G indicates the level of the defect in LIG, and I2D/G indicates the number of layers. The ID/G value was 0.29, which confirms the low lattice defects of the LIG prepared here [2D/G showed a value of 0.43, which is less than 1.0 [The multilayer LIG was well defined by the Raman spectrum, where only three D-, G-, and 2D-bands were observed. These three bands are shown in the Raman spectrum im e center . The dis defects . The secwn in −1 ,22, whilwn in −1 . Raman sred here ,24,25. Tthan 1.0 .−1, as shown in 2 of NiO, redox peaks appeared at a value of 0.52 and 0.2 V. There was also a broadening in the region between 0.4 and −0.7 V, as shown in Electrochemical measurements were carried out in a three-electrode configuration in an alkaline KOH electrolyte. The application was carried out for the three prepared electrodes  under the same conditions to evaluate their performance. Cyclic voltammetry (CV) curves were investigated at various scan rates between 5 and 100 mVs−1, where the higher current density exhibited faster charging, and vice versa. The maximum charging–discharging time of LIG-0 at 1.6 Ag−1 was 70 s, while it was 107 and 112 s for LIG-1 and LIG-2, respectively. However, it was observed that the LIG-2 electrode took a longer time (67 s) to be charged compared to LIG-1 (57 s), which took a longer time compared to the LIG-0 electrode (41 s). The observed behavior was due to the chemical modification of the LIG by NiO, where physical adsorption between the LIG material and NiO nanoparticles occurred. Thus, the electrode has a performance of oxidation and carbon materials, where the oxide and carbon materials perform both the pseudo-capacitance and EDLC mechanisms. The scribing of NiO by the laser generated a modification for the surface of the LIG. Thus, an increase in the charge capacity of the modified LIG by 200–300% compared to that of the raw LIG was observed.The behavior observed in the above CV curves was reflected and shown in the galvanostatic charge–discharge (GCD) curves, as shown in s) containing the resistance of the electrode materials, the ionic resistance of the electrolyte, and the contact resistance between the electrode and the current collector; and (2) the radius of the semicircle represents the electrode conductivity and the charge transfer resistance (Rct) of the electrode material. In the middle-frequency region, the oblique curve represents the Warburg impedance, which represents the diffusion/transport of ions in the electrolyte. The capacitive behavior of the electrode takes place on the curve in the low-frequency region. As we mention later, the electrochemical properties of graphene changed significantly due to NiO doping, as the capacitance increased to 174 F/g. The modeled values of Rs and Rct withdrawn from the Nyquist diagram are listed in t also showed a large change after doping, where it increased from 5 up to 22 Ω. The interesting is the semi-circle, which was largely demonstrated at a higher frequency for the doped electrodes. It was expected that in the case of pure LIG, the electrode would work as an EDLC supercapacitor, as indicated in the CV and GCD curves. In the EDLC mechanism, the electrolyte ions accumulate on the electrode surface to form a double layer charge. However, in the LIG doped with NiO, both pseudo-capacitance and EDLC mechanisms occurred.The electrical impedance spectroscopy (EIS) was measured in the range of 0.1 Hz to 1.0 MHz. The three electrodes presented typical AC impedance attributes of supercapacitors. −1 when ionic liquid, organic, and aqueous electrolytes were used [−1 at 5 mVs−1 for LIG-0 and decreased with an increase in the scan rate. The specific capacitances of the LIG-1 and LIG-2 were 152 Fg−1 and 174 Fg−1, respectively. It was observed that the NiO-doped LIG was still higher than that of the pristine LIG at all scan rates. −1 are 150, 148, and 52 Fg−1 for LIG-2, LIG-1, and LIG-0, respectively. With increasing the discharging current up to 3.3 Ag−1, the specific capacitances were 58, 32, and 15 Fg−1 for LIG-2, LIG-1, and LIG-0, respectively.The specific capacitance of graphene has been previously reported to be 75, 99, and 135 Fgere used ,28. Figu−1 and a specific power of 429 Wkg−1, the specific energy has maximum values of 5.3, 5.6, and 2.0 Whkg−1 for LIG-2, LIG-1, and LIG-0, respectively. The specific energy of the NiO-doped LIG increased about three times compared to that of LIG-0. With increasing current density, the specific energy decreased, while the specific power increased.Supercapacitors, electrochemical capacitors, double layer capacitors, or Farad capacitors are electrochemical components for storing energy through a symmetric electrode. It is a kind between a conventional capacitor and a battery, adopting a double layer and a pseudo-capacitor to store electrical energy. It has a high electrical power compared to batteries, which have a high energy. Often, in capacitors, there is no chemical reaction during the energy storage process, and thus it is reversible and enables us to recharge and discharge thousands of times. Supercapacitors have fast charging speeds and can reach more than 95% of their capacity within a short time. −1 is shown in −1 for the rest of the cycles. As shown in −1. It is obvious that LIG-0 started with high efficiency at 95% and continued at almost the same CE until the 1000th cycle. For LIG-1, the CE started at 90% for LIG-1 and improved with the 300th cycle to 96% to the 1000th cycle. For LIG-2, the CE value was 77% and gradually improved to 92% at the 1000th cycle. Despite doping graphene with a material that exhibits a Faradaic reaction, the electrodes still show a good electrochemical performance in terms of cycling, charging, and discharging.The specific capacitance measured for 1000 cycles of charging and discharging at 2.3 Ag2 laser can be proposed. As shown in the CVs of LIG-0, LIG-1, and LIG-2 presented in 2+ concentration due to the increase in NiO/graphene, which exposes the pseudocapacitive behavior. However, it is expected that there will be a trade-off between the conductivity  and pseudocapacitance (based on NiO) in the presence of extra NiO, which may lead to an increase in the resistance and reduce the current. It is observed in The doping mechanism of NiO-doped graphene through the CONiOOH+e− ,32. Thus2 at different charging currents or scan rates of the swipe voltage. Also, the high specific capacitance of LIG-PEDOT recorded a value of 115 F/g, compared to the present value of 174 F/g for NiO-doped LIG.2 laser. HRTEM confirmed the fabrication of multilayered graphene sheets using a CO2 laser. It has been clearly shown that the crystalline planes appear (002) mostly in this type of graphene, with a d-space of 0.33 nm. Also, through SAED, it was found that this graphene contained two planes of (002) and (100). The fabrication of multilayer graphene and NiO-doped graphene sheets was also confirmed by Raman spectra, where D, G, and 2D of graphene and scattering peaks of NiO. Electrodes with different concentrations of NiO were tested for their electrochemical properties as supercapacitors without any additional processing. A significant improvement was observed in the performance of the composite electrodes as the specific capacitance increased from 69 to 174 Fg−1 at a scanning rate of 5 mVs−1. The same performance was also observed in the case of the specific capacitance calculated from the charge and discharge curves, which had that the two concentrations of NiO showed almost the same specific capacitance values. In all electrodes, the lifecycle performance was excellent up to the thousandth cycle. The stored energy increased 3 times (from 2.0 to 5.6 Whkg−1 corresponding to a power of 429 WKg−1). We can conclude that the current combination strategy between oxide and graphene is suitable for improving the electrochemical properties of graphene and can be used for further studies in the future.In summary, we summarize an easy strategy to improve the capacitive performance of graphene by incorporating nickel oxide into its layers using direct laser technology. NiO fine particles of less than 50 nm were dropped on the fabricated graphene and scribed using a CO