N-acetylcysteine as a novel methacrylate-based resin cement component: effect on cell apoptosis and genotoxicity in human gingival fibroblasts.

BACKGROUND: N-acetylcysteine (NAC) reduces the cytotoxicity and genotoxicity induced by monomers leached from dental composite resins. Herein, we investigated the effects of methacrylate-based resin cement used in dental implant restoration on apoptosis and genotoxicity, as well as the antiapoptotic and antigenotoxic capabilities of its component, NAC. METHODS: The antioxidant NAC (0.1 or 1 wt.%) was experimentally incorporated into the methacrylate-based dental resin cement Premier®. The Premier® + NAC (0.1 or 1 wt.%) mixture was subsequently immersed into Dulbecco's modified Eagle's medium for 72 h, and used to treat human gingival fibroblasts (HGFs). The viability of HGFs was determined using the XTT assay. The formation of deoxyribonucleic acid (DNA) double-strand breaks (DNA-DSBs) was determined using a γ-H2AX assay. Reactive oxygen species (ROS), apoptosis, necrosis, and cell cycles were detected and analyzed using flow cytometry. RESULTS: The eluate of Premier® significantly inhibited HGF proliferation in vitro by promoting a G1-phase cell cycle arrest, resulting in cell apoptosis. Significant ROS production and DNA-DSB induction were also found in HGFs exposed to the eluate. Incorporating NAC (1 wt.%) into Premier® was found to reduce cell cytotoxicity, the percentage of G1-phase cells, cell apoptosis, ROS production, and DNA-DSB induction. CONCLUSION: Incorporating NAC (1 wt.%) into methacrylate-based resin cement Premier® decreases the cell cytotoxicity, ROS production, and DNA-DSBs associated with resin use, and further offers protective effects against the early stages of cell apoptosis and G1-phase cell cycle arrest in HGFs. Overall, our in vitro results indicate that the addition of NAC into methacrylate-based resin cements may have clinically beneficial effects on the cytotoxicity and genotoxicity of these materials.

Methacrylate Ester Monomers.

The Expert Panel for Cosmetic Ingredient Safety reviewed newly available studies since their original assessment in 2005, along with updated information regarding product types and concentrations of use, and confirmed that these 22 methacrylate ester monomers are safe as used in nail enhancement products in the practices of use and concentration as described in this report, when skin contact is avoided.

N-acetyl cysteine inhibits IL-1α release from murine keratinocytes induced by 2-hydroxyethyl methacrylate.

The hydrophilic compound 2-hydroxyethyl methacrylate (HEMA) is a major component of dental bonding materials, and it enhances the binding of resin-composites to biomolecules. However, HEMA is a well-known contact sensitizer. We reported previously that intradermal injection of HEMA induces the production of IL-1 locally in the skin. Keratinocytes are the first barrier against chemical insults and constitutively express IL-1α. In this study, we analyzed whether HEMA induces the production of inflammatory cytokines from murine keratinocyte cell line Pam212 cells. We demonstrated that HEMA induced the release of 17-kDa mature IL-1α and caused cytotoxicity. The activity of calpain, an IL-1α processing enzyme, was significantly higher in HEMA-treated cells. The thiol-containing antioxidant N-acetyl cysteine (NAC) inhibited HEMA-induced IL-1α release but not cytotoxicity. NAC inhibited intracellular calpain activity and reactive oxygen species (ROS) production induced by HEMA. NAC post-treatment also inhibited IL-1α release and intracellular ROS production induced by HEMA. Furthermore, HEMA-induced in vivo inflammation also inhibited by NAC. NAC inhibited polymerization of HEMA through adduct formation via sulfide bonds between the thiol group of NAC and the reactive double bond of HEMA. HEMA-induced IL-1α release and cytotoxicity were also inhibited if HEMA and NAC were pre-incubated before adding to the cells. These results suggested that NAC inhibited IL-1α release through decreases in intracellular ROS and the adduct formation with HEMA. We concluded that HEMA induces IL-1α release from skin keratinocytes, and NAC may be a promising candidate as a therapeutic agent against inflammation induced by HEMA.

Assessment of Mechanical/Chemical Properties and Cytotoxicity of Resin-Modified Glass Ionomer Cements Containing Sr/F-Bioactive Glass Nanoparticles and Methacrylate Functionalized Polyacids.

This study prepared low-toxicity, elemental-releasing resin-modified glass ionomer cements (RMGICs). The effect of 2-hydroxyethyl methacrylate (HEMA, 0 or 5 wt%) and Sr/F-bioactive glass nanoparticles (Sr/F-BGNPs, 5 or 10 wt%) on chemical/mechanical properties and cytotoxicity were examined. Commercial RMGIC (Vitrebond, VB) and calcium silicate cement (Theracal LC, TC) were used as comparisons. Adding HEMA and increasing Sr/F-BGNPs concentration decreased monomer conversion and enhanced elemental release but without significant effect on cytotoxicity. Rising Sr/F-BGNPs reduced the strength of the materials. The degree of monomer conversion of VB (96%) was much higher than that of the experimental RMGICs (21-51%) and TC (28%). The highest biaxial flexural strength of experimental materials (31 MPa) was significantly lower than VB (46 MPa) (p < 0.01) but higher than TC (24 MPa). The RMGICs with 5 wt% HEMA showed higher cumulative fluoride release (137 ppm) than VB (88 ppm) (p < 0.01). Unlike VB, all experimental RMGICs showed Ca, P, and Sr release. Cell viability in the presence of extracts from experimental RMGICs (89-98%) and TC (93%) was significantly higher than for VB (4%). Experimental RMGICs showed desirable physical/mechanical properties with lower toxicity than the commercial material.

Challenges in the classification of chemical respiratory allergens based on human data: Case studies of 2-hydroxyethylmethacrylate (HEMA) and 2-hydroxypropylmethacrylate (HPMA).

Occupational asthma resulting from workplace exposure to chemical respiratory allergens is an important disease. No widely accepted or formally validated tests for the identification of chemical respiratory sensitizers. Consequently, there is a heavy reliance on human data from clinical examinations. Unfortunately, however, although such investigations are critical for the diagnosis of occupational asthma, and in guiding remedial actions, they do not reliably identify specific chemicals within the workplace that are the causative agents. There are several reasons for this, including the fact that specific inhalation tests conducted as part of clinical investigations are frequently performed with complex mixtures rather than single substances, that sometimes inhalation challenges are conducted at concentrations above the OEL and STEL, where effects may be confounded by irritation, and that involvement of immune mechanisms cannot be assumed from the observation of late asthmatic reactions. Further, caution should be taken when implicating substances on lists of "recognised" asthmagens unless they have undergone a formal weight of evidence assessment. Here the limitations of clinical investigations as currently performed for the purposes of regulatory classification and decision making are explored by reference to previously published case studies that implicate 2-hydroxyethylmethacrylate (HEMA) and/or 2-hydroxypropylmethacrylate (HPMA) as respiratory allergens.

Toxicity assessment of core-shell and superabsorbent polymers in cell-based systems.

The identification of health risks arising from occupational exposure to submicron/nanoscale materials is of particular interest and toxicological investigations designed to assess their hazardous properties can provide valuable insights. The core-shell polymers poly (methyl methacrylate)@poly (methacrylic acid-co-ethylene glycol dimethacrylate) [PMMA@P (MAA-co-EGDMA)] and poly (n-butyl methacrylate-co-ethylene glycol dimethacrylate)@poly (methyl methacrylate) [P (nBMA-co-EGDMA)@PMMA] could be utilized for the debonding of coatings and for the encapsulation and targeted delivery of various compounds. The hybrid superabsorbent core-shell polymers poly (methacrylic acid-co-ethylene glycol dimethacrylate)@silicon dioxide [P (MAA-co-EGDMA)@SiO2] could be utilized as internal curing agents in cementitious materials. Therefore, the characterization of their toxicological profile is essential to ensure their safety throughout manufacturing and the life cycle of the final products. Based on the above, the purpose of the present study was to assess the acute toxic effects of the above mentioned polymers on cell viability and on cellular redox state in EA. hy926 human endothelial cells and in RAW264.7 mouse macrophages. According to our results, the examined polymers did not cause any acute toxic effects on cell viability after any administration. However, the thorough evaluation of a panel of redox biomarkers revealed that they affected cellular redox state in a cell-specific manner. As regards EA. hy926 cells, the polymers disrupted redox homeostasis and promoted protein carbonylation. Concerning RAW264.7 cells, P (nBMA-co-EGDMA)@PMMA caused disturbances in redox equilibrium and special emphasis was placed on the triphasic dose-response effect detected in lipid peroxidation. Finally, P (MAA-co-EGDMA)@SiO2 activated cellular adaptive mechanisms in order to prevent from oxidative damage.

Evidential requirements for the regulatory hazard and risk assessment of respiratory sensitisers: methyl methacrylate as an example.

This review addresses the need for a framework to increase the consistency, objectivity and transparency in the regulatory assessment of respiratory sensitisers and associated uncertainties. Principal issues are considered and illustrated through a case study (with methyl methacrylate). In the absence of test methods validated for regulatory use, formal documentation of the weight-of-evidence for hazard classification both at the level of integration of individual studies within lines of evidence and across a broad range of data streams was agreed to be critical for such a framework. An integrated approach is proposed to include not only occupational studies and clinical evidence for the regulatory assessment of respiratory sensitisers, but also information on structure and physical and chemical factors, predictive approaches such as structure activity analysis and in vitro and in vivo mechanistic and toxicokinetic findings. A weight-of-evidence protocol, incorporating integration of these sources of data based on predefined considerations, would contribute to transparency and consistency in the outcome of the assessment. In those cases where a decision may need to be taken on the basis of occupational findings alone, conclusions should be based on transparent weighting of relevant data on the observed prevalence of occupational asthma in various studies taking into account all relevant information including the range and nature of workplace exposures to the substance of interest, co-exposure to other chemicals and study quality.

TMT-based quantitative proteomic analysis reveals the underlying mechanisms of glycidyl methacrylate-induced 16HBE cell malignant transformation.

Glycidyl methacrylate (GMA) has been widely used as tackifying/crosslinking copolymer monomer in the industrial section. Occupational and environmental exposure to GMA is inevitable. GMA is classified as a Group 2 A carcinogen. However, it still lacks a sufficient understanding of its carcinogenicity at the protein level. The major pathways and players during the malignant transformation process remain unknown. In this study, we first established and characterized a malignant transformation model using human bronchial epithelial (16HBE) cells exposed to 8 µg/mL GMA. Then the proteomics approach, western-blot analysis as well as quantitative PCR (qPCR) analysis were employed to investigate its underlying mechanisms of carcinogenicity. Our results showed that the 16HBE cells exposed to GMA and passaged to the 40th generation had undergone a malignant transformation. Proteomic analysis revealed that 123 proteins were significantly up-regulated while 160 proteins were down-regulated during the process of malignant transformation. Importantly, further pathway analysis identified the extracellular matrix-receptor (ECM-receptor) interaction pathway to be one of the major players mediating the process and most of the differentially expressed proteins (DEPs) were up-regulated, including two vital proteins, CD44 and MMP14, as well as members from integrin family. These results provide direct proteomic evidence that DEPs related to the ECM-receptor interaction pathway play an active role in reinforcing the carcinogenicity of GMA. The findings of this study might deepen our understanding of the underlying mechanisms of GMA carcinogenicity and thus facilitate the risk assessment of GMA.

Toxicity of resin-matrix cements in contact with fibroblast or mesenchymal cells.

The main aim of this study was to perform an integrative review on the toxic effects of resin-matrix cements and their products in contact with fibroblasts or mesenchymal cells. A bibliographic search was performed on PubMed using the following search terms: "cytotoxicity" AND "fibroblast" OR "epithelial" OR "mesenchymal" AND "polymerization" OR "degree of conversion" OR "methacrylate" OR "monomer" AND "resin cement" OR "resin-based cement". The initial search in the available database yielded a total of 277 articles of which 21 articles were included in this review. A decrease in the viability of mouse fibroblasts ranged between 13 and 15% that was recorded for different resin-matrix cements after light curing exposure for 20 s. The viability of human fibroblasts was recorded at 83.11% after light curing for 20 s that increased up to 90.9% after light curing exposure for 40 s. Most of the studies linked the highest toxicity levels when the cells were in contact with Bis-GMA followed by UDMA, TEGDMA and HEMA. Resin-matrix cements cause a cytotoxic reaction when in contact with fibroblasts or mesenchymal cells due to the release of monomers from the polymeric matrix. The amount of monomers released from the resin matrix and their cytotoxicity depends on the polymerization parameters.

Oxymatrine attenuates TNBS-induced colinutis in rats through TLR9/Myd88/NF-κB signal pathway.

Objective: Due to its well-known anti-inflammatory property, oxymatrine (OMT) has received more attention on the aspect of treating ulcerative colitis. Although efforts have been undertaken to understand the therapeutic mechanism of OMT on ulcerative colitis (UC), the remedial principle is still ambiguous. Numerous studies have shown that TLR9/Myd88/NF-κB signal pathway played a key role in the pathogenesis of UC. Moreover, TLR9/Myd88/NF-κB signal pathway is a part of the most important pathways for regulating the immune response.Methods: We explored the influence of OMT with different dosages on UC by establishing a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. Moreover, the participation of TLR9/Myd88/NF-κB signal pathway and whether OMT protects against UC though targeting this pathway are further studied.Results: Our data revealed that OMT could significantly relieve the symptom of TNBS-induced colitis in rats by reactivating the tight junction protein and, more important, by inhibiting the activation of TLR9/Myd88/NF-κB pathway and protein expression levels of its downstream inflammatory factors.Conclusion: OMT could relieve colitis in rat models by impacting tight junction proteins' TLR9/Myd88/NF-κB signal pathways and activity.

Fabrication of 3D scaffolds based on fully biobased unsaturated polyester resins by microstereo-lithography.

Additive Manufacturing (AM) technologies are an effective route to fabricate tailor made scaffolds for tissue engineering (TE) and regenerative medicine, with microstereo-lithography (µSLA) being one of the most promising techniques to produce high quality 3D structures. Here, we report the crosslinking studies of fully biobased unsaturated polyesters (UPs) with 2-hydroxyethyl methacrylate (HEMA) as the unsaturated monomer (UM), using thermal and µSLA crosslinking processes. The resulting resins were fully characterized in terms of their thermal and mechanical properties. Determination of gel content, water contact angle, topography and morphology analysis by atomic force microscopy and scanning electron microscopy were also performed. The results show that the developed UP resins (UPRs) have promising properties for µSLA.In vitrocytotoxicity assays performed with 3T3-L1 cell lines showed that the untreated scaffolds exhibited a maximum cellular viability around 60%, which was attributed to the acidic nature of the UPRs. The treatment of the UPRs and scaffolds with ethanol (EtOH) improved the cellular viability to 100%. The data presented in this manuscript contribute to improve the performance of biobased UPs in AM.

Bifunctional Smart Hydrogel Dressing with Strain Sensitivity and NIR-Responsive Performance.

Smart response hydrogel has a broad application prospect in human health real-time monitoring due to its responses to a variety of stimuli. In this study, we developed a novel smart hydrogel dressing based on conductive MXene nanosheets and a temperature-sensitive PNIPAm polymer. γ-Methacryloxypropyltrimethoxysilane (KH570) was selected to functionalize the surface of MXene further to improve the interface compatibility between MXene and PNIPAm. Our prepared K-M/PNIPAm hydrogel was found to have a strain-sensitive property, as well as a respond to NIR phase change and volume change. When applied as a strain flexible sensor, this K-M/PNIPAm hydrogel exhibited a high strain sensitivity with a gauge factor (GF) of 4.491, a broad working strain range of ≈250%, a fast response of ∼160 ms, and good cycle stability (i.e., 3000 s at 20% strain). Besides, this K-M/PNIPAm hydrogel can be used as an efficient NIR light-controlled drug release carrier to achieve on-demand drug release. This work paved the way for the application of smart response hydrogel in human health real-time monitoring and NIR-controlled drug release functions.

Characteristics of experimental resin-modified glass-ionomer cements, containing alternate monomers to HEMA.

OBJECTIVE: Resin-modified glass ionomer cements (RMGICs) present several advantages (e.g. fluoride release), but their reported cytotoxicity has been associated with hydroxyethyl methacrylate (HEMA) monomer release. Therefore, different monomers were tested for use in RMGICs in order to improve their biocompatibility and reduce monomer release. METHODS: Eight experimental liquid compositions were prepared replacing different percentages of HEMA (conventional monomer used in commercial RMGICs) with hydroxypropyl-methacrylate (HPM) and/or tetrahydrofurfuryl-methacrylate (THFM), which are known to have better biocompatibility. Moreover, two commercial materials (Fuji-Plus and RelyX) and two compositions, based on these (home), were included as controls. Monomer release of all materials (commercial, home and experimental) were tested using high-performance liquid chromatography (HPLC) methods after immersing discs in deionized-water (DW) or ethanol:DW. Cytotoxicity of the materials extracts was tested on normal human oral fibroblast line (NHOF-1) using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. RESULTS: Three experimental materials containing THFM (F3, R3 and R4) showed less or similar monomer release compared to corresponding commercial products. Furthermore, two experimental materials (F3 and F4) showed similar effects on NHOF-1 cells compared to the negative control medium. SIGNIFICANCE: The lower monomer release and higher cell viability of some experimental THFM compositions are encouraging. THFM partially replacing HEMA is potentially a suitable alternative for producing biocompatible RMGICs.

Stretchable and Bioadhesive Gelatin Methacryloyl-Based Hydrogels Enabled by in Situ Dopamine Polymerization.

Hydrogel patches with high toughness, stretchability, and adhesive properties are critical to healthcare applications including wound dressings and wearable devices. Gelatin methacryloyl (GelMA) provides a highly biocompatible and accessible hydrogel platform. However, low tissue adhesion and poor mechanical properties of cross-linked GelMA patches (i.e., brittleness and low stretchability) have been major obstacles to their application for sealing and repair of wounds. Here, we show that adding dopamine (DA) moieties in larger quantities than those of conjugated counterparts to the GelMA prepolymer solution followed by alkaline DA oxidation could result in robust mechanical and adhesive properties in GelMA-based hydrogels. In this way, cross-linked patches with ∼140% stretchability and ∼19 000 J/m3 toughness, which correspond to ∼5.7 and ∼3.3× improvement, respectively, compared to that of GelMA controls, were obtained. The DA oxidization in the prepolymer solution was found to play an important role in activating adhesive properties of cross-linked GelMA patches (∼4.0 and ∼6.9× increase in adhesion force under tensile and shear modes, respectively) due to the presence of reactive oxidized quinone species. We further conducted a parametric study on the factors such as UV light parameters, the photoinitiator type (i.e., lithium phenyl-2,4,6-trimethylbenzoylphosphinate, LAP, versus 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, Irgacure 2959), and alkaline DA oxidation to tune the cross-linking density and thereby hydrogel compliance for better adhesive properties. The superior adhesion performance of the resulting hydrogel along with in vitro cytocompatibility demonstrated its potential for use in skin-attachable substrates.

Wound healing properties of triple cross-linked poly (vinyl alcohol)/methacrylate kappa-carrageenan/chitooligosaccharide hydrogel.

To develop an effective and mechanically robust wound dressing, a poly (vinyl alcohol) (PVA)/methacrylate kappa-carrageenan (κ-CaMA) composite hydrogel encapsulated with a chitooligosaccharide (COS) was prepared in a cassette via repeated freeze/thaw cycles, photo-crosslinking, and chemical cross-linking. The chemical, physical, mechanical, in vitro biocompatibility, in vivo wound-healing properties, and antibacterial activity of triple-crosslinked hydrogel were subsequently characterized. The results showed that the PVA/κ-CaMA/COS (Pκ-CaC) hydrogel had a uniformly thick, highly porous three-dimensional architecture with uniformly distributed pores, a high fluid absorption, and retention capacity without disturbing its mechanical stability, and good in vitro biocompatibility. Macroscopic images from the full-thickness skin wound model revealed that the wounds dressed with the proposed Pκ-CaC hydrogel were completely healed by day 14, while the histomorphological results confirmed full re-epithelization and rapid skin-tissue remodeling. This study thus indicates that the composite Pκ-CaC hydrogel has significant potential for use as a wound dressing.

Incorporation of dimethyl sulfoxide into experimental hydrophilic and hydrophobic adhesive resins: evaluation of cytotoxic activities.

This study evaluated the cytotoxicity of methacrylate-based resins containing dimethyl sulfoxide (DMSO). DMSO was incorporated into hydrophobic (R2) and hydrophilic (R5) resins at weight concentrations of 0, 0.01, 0.1, 1, 5, or 10 w/w %. Resin discs (n = 10/group) were prepared. Human gingival fibroblasts (HGF-1) were exposed to resin eluates for 24 h. Furthermore, dentin barrier test was performed using 3-D cultures of odontoblast-like cells (SV40 transfected pulp derived cells) with dentin slices of 400 µm thickness (n = 8). After acid etching of dentin, DMSO-modified resins were applied into the cavity part of the device and light-cured for 20 s. Cell viability (%) was assessed by MTT and analyzed spectrometrically. Data were analyzed by ANOVA and Tukey test (α = 0.05). Resin eluates showed statistically significantly lower % cell viability for all neat and DMSO-modified resins than seen for the negative control. Moreover, DMSO-R5 eluates resulted in significantly lower % cell viability than DMSO-R2 emulates. The dentin barrier test showed that DMSO-R2 did not result in significantly lower % cell viability, whereas incorporation of 1-10 w/w % DMSO into R5 resulted in significantly lower % of cell viability. Incorporating DMSO into hydrophilic self-etching resins may increase cytotoxicity. The biocompatibility is not influenced by the addition of DMSO into hydrophobic resin.

Aligned Graphene Mesh-Supported Double Network Natural Hydrogel Conduit Loaded with Netrin-1 for Peripheral Nerve Regeneration.

The gold standard treatment for peripheral nerve injuries (PNIs) is the autologous graft, while it is associated with the shortage of donors and results in major complications. In the present study, we engineer a graphene mesh-supported double-network (DN) hydrogel scaffold, loaded with netrin-1. Natural alginate and gelatin-methacryloyl entangled hydrogel that is synthesized via fast exchange of ions and ultraviolet irradiation provide proper mechanical strength and excellent biocompatibility and can also serve as a reservoir for netrin-1. Meanwhile, the graphene mesh can promote the proliferation of Schwann cells and guide their alignments. This approach allows scaffolds to have an acceptable Young's modulus of 725.8 ± 46.52 kPa, matching with peripheral nerves, as well as a satisfactory electrical conductivity of 6.8 ± 0.85 S/m. In addition, netrin-1 plays a dual role in directing axon pathfinding and neuronal migration that optimizes the tube formation ability at a concentration of 100 ng/mL. This netrin-1-loaded graphene mesh tube/DN hydrogel nerve scaffold can significantly promote the regeneration of peripheral nerves and the restoration of denervated muscle, which is even superior to autologous grafts. Our findings may provide an effective therapeutic strategy for PNI patients that can replace the scarce autologous graft.

The activity of methacrylate esters in skin sensitisation test methods II. A review of complementary and additional analyses.

Allergic contact dermatitis is an important occupational health issue, and there is a need to identify accurately those chemicals that have the potential to induce skin sensitisation. Hazard identification was performed initially using animal (guinea pig and mouse) models. More recently, as a result of the drive towards non-animal methods, alternative in vitro and in silico approaches have been developed. Some of these new in vitro methods have been formally validated and have been assigned OECD Test Guideline status. The performance of some of these recently developed in vitro methods, and of 2 quantitative structure-activity relationships (QSAR) approaches, with a series of methacrylate esters has been reviewed and reported previously. In this article that first review has been extended further with additional data and complementary analyses. Results obtained using in vitro methods (Direct Peptide Reactivity Assay, DPRA; ARE-Nrf2 luciferase test methods, KeratinoSens and LuSens; Epidermal Sensitisation Assay, EpiSensA; human Cell Line Activation Test, h-CLAT, and the myeloid U937 Skin Sensitisation test, U-SENS), and 2 QSAR approaches (DEREK™-nexus and TIMES-SS), with 11 methacrylate esters and methacrylic acid are reported here, and compared with existing data from the guinea pig maximisation test and the local lymph node assay. With this series of chemicals it was found that some in vitro tests (DPRA and ARE-Nrf2 luciferase) performed well in comparison with animal test results and available human skin sensitisation data. Other in vitro tests (EpiSensA and h-CLAT) proved rather more problematic. Results with DEREK™-nexus and TIMES-SS failed to reflect accurately the skin sensitisation potential of the methacrylate esters. The implications for assessment of skin sensitising activity are discussed.

Genotoxic and cytotoxic potential of methacrylate-based orthodontic adhesives.

OBJECTIVES: The biocompatibility of methacrylate-based adhesives is a topic that is intensively discussed in dentistry. Since only limited evidence concerning the cyto- and genotoxicity of orthodontic adhesives is available, the aim of this study was to measure the genotoxic potential of seven orthodontic methacrylate-based adhesives. MATERIALS AND METHODS: The XTT assay was utilized to determine the cytotoxicity of Assure Plus, Assure Bonding Resin, ExciTE F, OptiBond Solo Plus, Scotchbond Universal Adhesive, Transbond MIP, and Transbond XT after an incubation period of 24 h on human gingival fibroblasts. We also performed the γH2AX assay to explore the genotoxic potential of the adhesives within cytotoxic dose ranges after an incubation period of 6 h. RESULTS: The XTT assay showed a concentration-dependent reduction in cell viability. The decrease in cellular viability was in the same dose range most significant for Assure Plus, rendering it the adhesive material with the highest cytotoxicity. Employing the γH2AX assay, a concentration-dependent increase in H2AX phosphorylation was detected, indicating induction of DNA damage. CONCLUSIONS: For most products, a linear correlation between the material concentration and γH2AX foci was observed. The most severe effect on γH2AX focus induction was found for Transbond MIP, which was the only adhesive in the test group containing the co-initiator diphenyliodonium hexafluorophosphate (DPIHP). CLINICAL RELEVANCE: The data indicate that orthodontic adhesives, notably Transbond MIP, bear a genotoxic potential. Since the study was performed with in vitro cultivated cells, a direct translation of the findings to in vivo exposure conditions should be considered with great diligence.

Reduced graphene oxide-GelMA-PCL hybrid nanofibers for peripheral nerve regeneration.

Graphene oxide is currently used in peripheral nerve engineering but has certain limitations, such as cytotoxicity and lack of electrical conductivity, both of which are crucial in regulating nerve-associated cell behaviors. In this work, we engineered reduced graphene oxide-GelMA-PCL nanofiber nerve guidance conduits via electrospinning. rGO incorporated into the GelMA/PCL matrix significantly enhanced the electrical conductivity and biocompatibility of the hybrid materials. In addition, hybrid nanofibers with low concentrations of rGO (0.25 and 0.5 wt%) could significantly improve the proliferation of Schwann cells (RSC96). More importantly, rGO/GelMA/PCL hybrid nanofibers could activate the epithelial-mesenchymal transition (EMT)-related gene expression of Schwann cells (RSC96). From the in vivo study, it was observed that rGO/GelMA/PCL nerve guidance conduits could promote both sensory/motor nerve regeneration and functional recovery in rats. Our composite strategy of combining rGO within a biocompatible nanofiber scaffold is simple but effective in improving tissue engineering outcomes. The rGO/GelMA/PCL hybrid nanofibers have great potential in peripheral nerve tissue engineering. They will also provide an experimental basis for the development of further electrical stimulation in peripheral nerve regeneration.