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Introduction: The management of apical periodontitis involves the elimination of bacteria to achieve healing of the periapical tissues. To this end, understanding of the antimicrobial properties and cytotoxicity of root canal sealers over time is important. This study aimed to assess the cytocompatibility and antibacterial activity of leachates obtained from selected endodontic sealers., Methods: Four sealers were used in this study; AH Plus, an epoxy resin-based sealer, and three hydraulic calcium silicate-based sealers: AH Plus Bioceramic, BioRoot RCS, and BioRoot Flow. Sealer chemistry was assessed by scanning electron microscopy and energy dispersive spectrum analysis. Leachates of the tested sealers were prepared by immersing sealer discs in Hank's balanced salt solution for 28 and 90 days. Element release was assessed using inductively coupled plasma mass spectroscopy. Enterococcus faecalis and Fusobacterium nucleatum were exposed to the leachates followed by colony-forming unit determination, and the human osteoblast-like cell line Saos-2 was assessed with regard to cell death, caspase expression and activity of alkaline phosphatase (ALP) after stimulation with the leachates., Results: Calcium leaching was detected in the tricalcium silicate-based sealers, which increased the leachate pH significantly (P < .0001). AH Plus Bioceramic leachate displayed antimicrobial activity at 28 days against E. faecalis (P < .01). ALP levels were reduced in response to AH Plus Bioceramic and BioRoot RCS 1-day leachates (P < .05). High cell viability was observed after exposure to all sealers., Conclusions: The leachates of the tested sealers were cytocompatible; however, their antimicrobial activity as well as their potential to induce the bone formation marker ALP was minimal., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The deposition of nanoplastics in the environment poses a direct threat to human health through the food chain. There is an urgent need to investigate how they can be effectively removed from water. In this work, the toxic effects of nanopolystyrene (PS) at different concentrations on Phaeodactylum tricornutum (PT) were investigated. The results show that PS affects the cell activity of PT through cell wall adhesion and shading effect and hinders the transmission of light energy, thus inhibiting the growth of PT. Considering that living PT is not suitable for the removal of heterogeneous aggregation of PS, magnesium silicate (MS) was obtained by calcination of PT biomass based on retaining salt. The maximum adsorption capacity of PS by MS was 40.85 mg g -1 , which was 10 times higher than that of conventional adsorbents. The presence of competitive anions significantly affects the removal of PS. The application in real water bodies and the reusability of the adsorbents were also verified. By characterizing the materials before and after adsorption, it is found that the adsorption mechanism mainly includes electrostatic attraction, hydrogen bonding, π-π interaction, and complexation between Si-O bond and PS. This study explains the toxic effect of nano-PS on PT and innovatively develops a biomass derivative from diatoms, which provides a novel and feasible strategy for environmental remediation.

Background: An ideal aesthetic restorative material should be attached to the tooth tissues by adhesion, have a smooth surface as possible, should not cause toxic reactions in the pulp and discoloration and microleakage. This study aims at comparatively assess the cytotoxicity of current adhesive systems on human dental pulp cells., Materials and Methods: The adequate density of human pulp cells was observed from the ready cell line. The passaging was performed and the 3rd passage cells were selected. Adhesive systems and MTA were used on the cultures. Trypan blue staining was conducted on the cells at the 1st, 2nd, 3rd days and a count of live and dead cells using a light microscope. The dead cells whose membrane integrity was impaired by staining with trypan blue and the viability rate was determined using live and dead cell numbers. Data analysis was performed using IBM SPSS Statistics 22., Results: A significant difference in vialibity rates between adhesive systems was observed on the first day. No significant statistical differences were observed on the 2nd and 3rd days (p < 0.05)., Conclusion: Futurabond M showed similar biocompatibility with MTA on human pulp cells and it can be applied in cavities with 1-1.5 mm hard tissue between pulp and dentine., (© 2024. The Author(s).)

Testing the biocompatibility of commercially available dental materials is a major challenge in dental material science. In the present study, the biocompatibility of four commercially available dental materials Mineral Trioxide Aggregate, Biodentine, Harvard BioCal-CAP and Oxford ActiveCal PC was investigated. The biocompatibility analysis was performed on zebrafish embryos and larvae using standard toxicity tests such as survivability and hatching rates. Comparative toxicity analysis of toxicity was performed by measuring apoptosis using acridine orange dye and whole mount immunofluorescence methods on zebrafish larvae exposed to the dental materials at different dilutions. Toxicity analysis showed a significant decrease in survival and hatching rates with increasing concentration of exposed materials. The results of the apoptosis assay with acridine orange showed greater biocompatibility of Biodentine, Oxford ActiveCal PC, Harvard BioCal-CAP and Biodentine compared to MTA, which was concentration dependent. Consequently, this study has shown that showed resin-modified calcium silicates are more biocompatible than traditional calcium silicates., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Karahan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: The present study examined the leaching and cytotoxicity of bismuth from ProRoot MTA and aimed to identify whether bismuth leaching was affected by the cement base and the immersion regime used., Methodology: The leaching profile of bismuth was examined from ProRoot MTA and compared with hydroxyapatite containing 20% bismuth oxide as well as hydroxyapatite and tricalcium silicate to investigate whether bismuth release changed depending on the cement base. Bismuth leaching was determined after 30 and 180 days of ageing immersed in Dulbecco's modified Eagle's medium (DMEM) using mass spectroscopy (ICP-MS). The media were either unchanged or regularly replenished. The pH, surface microstructure and phase changes of aged materials were assessed. Wistar rat femoral bone marrow stromal cells (BMSCs) and cutaneous fibroblasts were isolated, cultured and seeded for cell counting (trypan blue live/dead) after exposure to non-aged, 30- and 180-days-aged samples in regularly replenished DMEM. Aged DMEM in contact with materials was also used to culture BMSCs to investigate the effect of material leachates on the cells. Gene expression analysis was also carried out after direct exposure of cells to non-aged materials. Differences between groups were statistically tested at a significance level of 5%., Results: All materials exhibited alterations after immersion in DMEM and this increased with longer exposure times. The bismuth leached from ProRoot MTA as detected by ICP-MS. Aged ProRoot MTA samples exhibited a black discolouration and surface calcium carbonate deposition. ProRoot MTA influenced cell counts after direct exposure and its 180-days leachates reduced BMSC viability. After direct BMSC contact with non-aged ProRoot MTA an upregulation of metallothionein (MT1 and MT2A) expression and down-regulation of collagen-1a (Col-1a) and bone sialoprotein (BSP) expression was identified., Conclusions: Bismuth leaching was observed throughout 180-days observation period from all materials containing bismuth oxide. This negatively influenced cell viability and gene expression associated with bismuth exposure. This is the first study to report that metallothionein gene expression was influenced by exposure to ProRoot MTA., (© 2024 The Author(s). International Endodontic Journal published by John Wiley & Sons Ltd on behalf of British Endodontic Society.)

Objective: Several materials have been developed to preserve pulp vitality. They should have ideal cytocompatibility characteristics to promote the activity of stem cells of human exfoliated deciduous teeth (SHED) and thus heal pulp tissue., Objective: To evaluate the cytotoxicity of different dilutions of bioceramic material extracts in SHED., Methodology: SHED were immersed in αMEM + the material extract according to the following experimental groups: Group 1 (G1) -BBio membrane, Group 2 (G2) - Bio-C Repair, Group 3 (G3) - MTA Repair HP, Group 4 (G4) - TheraCal LC, and Group 5 (G5) - Biodentine. Positive and negative control groups were maintained respectively in αMEM + 10% FBS and Milli-Q Water. The methods to analyze cell viability and proliferation involved MTT and Alamar Blue assays at 24, 48, and 72H after the contact of the SHED with bioceramic extracts at 1:1 and 1:2 dilutions. Data were analyzed by the three-way ANOVA, followed by Tukey's test (p<0.05)., Results: At 1:1 dilution, SHED in contact with the MTA HP Repair extract showed statistically higher cell viability than the other experimental groups and the negative control (p<0.05), except for TheraCal LC (p> 0.05). At 1:2 dilution, BBio Membrane and Bio-C showed statistically higher values in intra- and intergroup comparisons (p<0.05). BBio Membrane, Bio-C Repair, and Biodentine extracts at 1:1 dilution showed greater cytotoxicity than 1:2 dilution in all periods (p<0.05)., Conclusion: MTA HP Repair showed the lowest cytotoxicity even at a 1:1 dilution. At a 1:2 dilution, the SHED in contact with the BBio membrane extract showed high cell viability. Thus, the BBio membrane would be a new non-cytotoxic biomaterial for SHED. Results offer possibilities of biomaterials that can be indicated for use in clinical regenerative procedures of the dentin-pulp complex.

Aim: The objective of this in-vitro study was to assess the cytotoxicity and alkaline phosphatase (ALP) activity of curcumin and aloin extracted from Curcuma longa and Aloe vera , and mineral trioxide aggregate (MTA) on human dental pulp stem cells., Methods: Human dental pulp stem cells (Lonza Group, Switzerland), curcumin (Sigma-Aldrich, USA), aloin (Sigma-Aldrich, USA), and ProRoot MTA (Dentsply, USA) were used in the study. 2.5-6.75-12.5-25-50 μg/ml of curcumin and aloin, 25%-50%-75%-100% of MTA were prepared; pulp cells unincubated with a material were assessed as controls. Cytotoxicity of all doses/concentrations of materials was analysed on days of 1, 2, 3, and 7 by WST-1 test. 2.5-6.75 μg/ml of curcumin and aloin, 25%-50% of MTA incubated with cells for 7-14 days were evaluated for ALP activity by ELISA test. Data was statistically analysed by One Way ANOVA, Tukey, and Sidak tests at GraphPad Prism 6., Results: The findings have shown that 2.5 μg/ml of curcumin, all doses of aloin, 25% and 50% of MTA increased cell proliferation significantly on day 1 ( P < 0.05). Curcumin, aloin, and MTA decreased the cell viability as dose/concentration and exposure time increased. All materials have shown no significant increases in ALP activity ( P > 0.05) on 7 and 14 days., Conclusion: Data of this study revealed that 2.5 - 6.75 μg/ml of curcumin/aloin, 25%-50% of MTA have promoted cell viability and proliferation of human dental pulp cells; and none of the materials have significantly increased the ALP activity at 7-14 days., (Copyright © 2024 Copyright: © 2024 Indian Journal of Dental Research.)

The aim of this study was to evaluate cytotoxicity and genotoxicity of calcium-silicate based sealers and comparing them with a gold standard-an epoxy-based sealant. Two experimental cell lines were used, gingival fibroblasts (hGF) and monocyte/macrophage peripheral blood cell line (SC). The cytotoxicity (XTT assay) and genotoxicity (comet assay) were evaluated both after 24-h and 48-h incubation. Additionally, after 48-h incubation, the cell apoptosis and cell cycle progression was detected. BioRoot Flow induced a significant decrease in hGF cells viability compared to the negative control groups both after 24-h (p < 0.001) and 48-h incubation (p < 0.01). In group with SC cells, after 24-h incubation significant increase in cells viability was detected for AH Plus Bioceramic Sealer in comparison to negative control (p < 0.05). BioRoot Flow and BioRoot RCS can be considered potentially genotoxic for the hGF cells after 48-h incubation (> 20% DNA damage). BioRoot Flow and BioRoot RCS, may have potential genotoxic effects and induce apoptosis in hGF cells which may irritate periapical tissues, resulting in a delayed healing. The findings of the study would be useful in selection of an appropriate sealant for root canal filling without causing cytotoxicity and genotoxicity., (© 2024. The Author(s).)

Background: As calcium silicate-based cements (CSCs) have found success in various vital pulp therapy applications, several new CSC products have emerged. This study aimed to assess the genotoxicity, cytotoxicity, and bioactivity of four CSCs by comparing the newly introduced materials Bio MTA+ and MTA Cem with previously studied materials, Biodentine and NeoMTA., Methods: Genotoxicity was evaluated using the micronucleus (MN) assay in human peripheral blood lymphocyte cells, measuring MN frequency and nuclear division index (NDI). Cytotoxicity was assessed in human dental pulp stem cells through the Water-Soluble Tetrazolium Salt-1 (WST-1) colorimetric assay. Bioactivity was determined by ELISA, measuring the levels of angiogenic and odontogenic markers (BMP-2, FGF-2, VEGF, and ALP). Statistical analyses included ANOVA, Dunnet and Sidak tests, and Wald chi-square test. (p < .05)., Results: The MN frequency in the groups was significantly lower than that in the positive control group (tetraconazole) (p < .05). NDI values decreased with increasing concentration (p < .05). Bio MTA+ and NeoMTA showed decreased cell viability at all concentrations in 7-day cultures (p < .01). All materials increased BMP-2, FGF-2, and VEGF levels, with Biodentine and NeoMTA showing the highest levels of BMP-2 and FGF-2 on day 7. Biodentine displayed the highest VEGF levels on day 7. Biodentine and NeoMTA groups exhibited significantly higher ALP activity than the Bio MTA+ and MTA Cem groups by day 7., Conclusion: Bio MTA+ and MTA Cem demonstrated no genotoxic or cytotoxic effects. Moreover, this study revealed bioactive potentials of Bio MTA+ and MTA Cem by enhancing the expression of angiogenic and osteogenic growth factors., (© 2024. The Author(s).)

The purpose of this study was to assess the effect of a calcium silicate-based sealers (CeraSeal) and an epoxy resin-based sealer (AH Plus) on cytotoxicity and cell migration of stem cell from the human apical papilla (hSCAPs) by using the Alamar Blue, Annexin V-FICT and wound healing assays. In Alamar Blue assay, hSCAPs exposed to undiluted CeraSeal extract had significantly higher cell viability compared with that observed when cells were treated with AH Plus in all experimental period (p < 0.001). The flow cytometry analysis confirmed the comparison on viable cells and indicated that AH Plus increased apoptosis compared to CeraSeal and the control groups (p < 0.001). Additionally, AH Plus exhibited significantly lower level of cell migration than CeraSeal and the control for up to 48 h observation (p < 0.01). In summary, calcium silicate-based sealer (CeraSeal) is less cytotoxic and more biocompatible than epoxy resin-based sealer (AH Plus)., (© 2023 Australian Society of Endodontology Inc.)

Aim: This study aimed to evaluate the cytotoxicity, biocompatibility and osteoinductive profile of a mineral trioxide aggregate (MTA)-hydrogel-based material (MTA Flow) in comparison with MTA Angelus., Methodology: Cell viability was evaluated in human periodontal ligament stem cells (hPDLSCs) using the methyl-thiazol-tetrazolium (MTT) colourimetric assay. Polyethylene tubes containing the tested materials and empty polyethylene tubes (control) were implanted in the subcutaneous tissue of Wistar rats. Cellular (lymphocyte infiltration) and extracellular events (ECM; collagen fibres) were analysed in histological sections. Immunohistochemical (collagen I, osteopontin, bone sialoprotein, bone morphogenetic protein4) analyses were also performed., Results: At 24, 48 and 72 h, all tested groups showed cell viability similar to control (p > .05). Regarding biocompatibility, all groups showed similar cellular events represented by a slight inflammatory reaction characterized by hyperaemia and a mild lymphocytic inflammatory infiltrate. The analysis of lymphocytes during the time showed a decrease in these cells in the control group and a significant interaction between MTA Angelus and control (p < .001), with MTA Angelus showing a more extensive inflammatory infiltrate. Regarding fibres, an increase in content was observed in all groups during the experimental time (7, 30 and 60 days), however, no difference was detected among the experimental groups (p = .063). After 60 days, the immunoexpression of bone matrix proteins in the MTA Flow group was similar to or higher than that observed in the MTA Angelus and in the control group., Conclusions: MTA Flow showed a non-cytotoxic behaviour, biocompatibility and ability to stimulate tissue mineralization., (© 2023 British Endodontic Society. Published by John Wiley & Sons Ltd.)

Sodium silicate (Na2SiO 3 ) is an inorganic silica salt used in many products. Few studies reported autoimmune diseases (AIDs) due to Na2SiO 3 exposure. This study investigates the role of Na2SiO 3 exposure by different routes and doses in AID development in rats. We assigned 40 female rats to four groups: G1 control group, G2 rats were subcutaneously injected with 5 mg Na2SiO 3 suspension, and G3 and G4 rats were orally administered 5 mg and 7 mg Na2SiO 3 suspension, respectively. Na2SiO 3 was administered weekly for 20 weeks. Serum anti-nuclear antibodies (ANA) detection, histopathology of kidney, brain, lung, liver, and heart, oxidative stress biomarkers (MDA and GSH) in tissues, Matrix metalloproteinase activity in serum, TNF-α, and Bcl-2 expression in tissues were performed. ANA was significantly increased in silicate groups, especially G2. Creatinine was significantly increased in silicate groups. Histopathology revealed vasculitis and fibrinoid degeneration of blood vessels, a picture of immune-mediated glomerulonephritis in the kidneys, and chronic interstitial pneumonia with medial hypertrophy of pulmonary blood vessels. The activity of gelatinases (MMP-2 and MMP-9) and collagenase (MMP-13), which play role in inflammation, remodeling, and immune complex degradation, were significantly increased in the silicate-exposed groups. Bcl-2 was significantly decreased, indicating apoptosis. Therefore, oral administration and subcutaneous injection of Na2SiO 3 induced immune-mediated glomerulonephritis with elevated ANA levels and overexpression of TNF-α in rats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The aim was to evaluate in vitro cytotoxicity and genotoxicity of Bio-C Repair (BCR), compared to Endosequence BC Root Repair (ERRM), MTA Angelus (MTA-Ang), and MTA Repair HP (MTA-HP). MC3T3 osteoblastic cells were exposed to extracts of the repairing bioceramic cements. After 1, 3, and 7 days, cytotoxicity and genotoxicity were evaluated by MTT and Micronucleus tests, respectively. Cells not exposed to biomaterials were used as a negative control. Data were compared using ANOVA two-way, followed by the Tukey Test (α=5%). MTA-Ang and MTA-HP showed no difference in relation to control regarding cytotoxicity in any experimental times. BCR and ERRM reduced cell viability after 3 and 7 days (p<0.05); however, the reduction caused by BCR was less than that caused by ERRM. Considering the micronucleus formation, all biomaterials caused an increase after 3 and 7 days (p<0.05), being greater for the BCR and ERRM groups. It can be concluded that BCR is non-cytotoxic in osteoblastic cells, as well as MTA-Ang e MTA Repair HP. BCR and ERRM showed greater genotoxicity than others tested biomaterials.

The aim of this study was to evaluate the physicochemical properties, cytotoxicity and bioactivity of a ready-to-use bioceramic material, Bio-C Repair (Angelus), in comparison with White MTA (Angelus) and Biodentine (Septodont). The physicochemical properties of setting time, radiopacity, pH, solubility, dimensional and volumetric changes were evaluated. Biocompatibility and bioactivity were assessed in Saos-2 osteoblast cell cultures by the MTT assay 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), Neutral Red (NR), Alizarin Red (ARS), and cell migration tests. Statistical analysis was performed by ANOVA, Tukey or Bonferroni tests (α = 0.05). Bio-C Repair had the longest setting time (p < 0.05), but radiopacity and solubility were accordance with the ISO 6876/2012 standards, besides linear expansion. Bio-C Repair and MTA had similar volumetric change (p > 0.05); lower than Biodentine (p < 0.05). All the materials evaluated had an alkaline pH. Bio-C Repair was cytocompatible and promoted mineralized nodule deposition in 21 days and cell migration in 3 days. In conclusion, Bio-C Repair had adequate radiopacity above 3mm Al, solubility less than 3%, dimensional expansion, and low volumetric change. In addition, Bio-C Repair promoted an alkaline pH and presented bioactivity and biocompatibility similar to MTA and Biodentine, showing potential for use as a repair material.

Engineered silver nanoparticles (AgNPs), including silver silicate nanoparticles (Ag-SiO 2 NPs), are used in a wide variety of medical and consumer applications. Inhaled AgNPs have been found to translocate to the olfactory bulb (OB) after inhalation and intranasal instillation. However, the biological effects of Ag-SiO 2 NPs and their potential nose-to-brain transport have not been evaluated. The present study assessed whether inhaled Ag-SiO 2 NPs can elicit microglial activation in the OB. Adult Sprague-Dawley rats inhaled aerosolized Ag-SiO 2 NPs at a concentration of 1 mg/ml for 6 hours. On day 0, 1, 7, and 21 post-exposure, rats were necropsied and OB were harvested. Immunohistochemistry on OB tissues were performed with anti-ionized calcium-binding adapter molecule 1 and heme oxygenase-1 as markers of microglial activation and oxidative stress, respectively. Aerosol characterization indicated Ag-SiO 2 NPs were sufficiently aerosolized with moderate agglomeration and high-efficiency deposition in the nasal cavity and olfactory epithelium. Findings suggested that acute inhalation of Ag-SiO 2 NPs elicited transient and differential microglial activation in the OB without significant microglial recruitment or oxidative stress. The delayed and differential pattern of microglial activation in the OB implied that inhaled Ag-SiO 2 may have translocated to the central nervous system via intra-neuronal pathways.

Natural Layered Silicates (NLS) and Synthetic Layered Silicates (SLS) are a diverse group of clay minerals that have attracted great interest in various branches of industry. However, despite growing demand for this class of material, their impact on human health has not been fully investigated. Therefore, the aim of this study was to evaluate and compare the potential toxic effects of a wide range of commercially available SLS and NLS of varying physicochemical properties (lithium (Li) or fluoride (F) content and size). Mouse BALB/c monocyte macrophage (J774A.1) and human monocyte-derived macrophages (MDMs) were chosen as in vitro models of alveolar macrophages. Montmorillonite, hectorite, Medium (med) F/High Li and Low F/Med Li particles, were cytotoxic to cells and induced potent pro-inflammatory responses. The remaining particles (No F/Very (V)Low Li, No F/Med Li, No F/Low Li, High F/Med Li and High F/Med Li washed) were non- to relatively low- cytotoxic and inflammogenic, in both type of cells. In an acellular condition none of the tested samples increased reactive oxygen species (ROS), while ROS generation was observed following exposure to sublethal concentrations of Med F/High Li, Low F/Med Li, montmorillonite and hectorite samples, in J774A.1 cells. Based on the results obtained in this study the toxic potency of tested samples was not associated with lithium or fluoride content, but appeared to be dependent on particle size, with the platelets of larger dimension and lower surface area being more potent than the smaller platelet particles with higher surface area. In addition, the increased bioactivity of Med F/High Li and Low F/Med Li was associated with endotoxin contamination. Obtained results demonstrated that layered silicate materials have different toxicological profiles and suggest that toxicological properties of a specific layered silicate should be investigated on an individual basis., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: To examine the cytotoxicity and genetic expression of SHEDs cultured in eluates of various calcium silicate based pulpotomy materials., Study Design: MTT assay, flow cytometry, alizarin red staining and scratch assay was used to assess the cellular viability, apoptosis, calcium matrix deposits and cell migration respectively. The gene expression of ALP, OCN and BMP -2, were measured with rtPCR. One way ANNOVA and Bonferroni post test was used for statistical analysis., Results: MTT assay analysis reported that all the test specimen had no cytotoxic effects. The highest number of live cells [ % ] was found in RetroMTA. The highest percentage of cell migration was observed in SHEDs cultured in EndoCem Zr. The mean absorbance for calcium matrix deposition was higher or similar in all test specimens, when compared to control groups. The expression of BMP -2 and OCN were significantly higher in cells exposed to RetroMTA and NeoMTA respectively after 24 hrs of incubation. After 72 hrs of incubation the mRNA expression of ALP was significantly higher in MTA., Conclusions: SHEDs cultured in eluates of various calcium silicate based cements exhibited cytocompatibility and maintained odontogenic like phenotype differentiation in SHEDs.

This study investigated the cytotoxicity and release of Transforming Growth Factor Beta 1 (TGF-β1) from cultured human apical papilla cells (APCs) after application of four bioactive materials. Culture of APCs was established and used for cytotoxic and quantitative assays. Extracts of Biodentine, Bio-C Repair, MTA Repair and White MTA were prepared and diluted (1, 1:4 and 1:16) and used for MTT assays up to 72 h. Total TGF-β1 was quantified by ELISA. Data were analyzed by ANOVA and Tukey's test (α = 0.05). For Biodentine, at 24 h and 48 h, cell viability was lower than control (p < 0.05). At 72 h, only undiluted extract of Biodentine were cytotoxic (p < 0.05). At 24 h, a cytotoxic effect was found for undiluted and 1:4 dilution of Bio-C Repair (p < 0.05). At 48 h, however, Bio-C Repair at 1:4 and 1:8 dilution showed higher cell viability (p < 0.05). At 24 and 48 h, the cell viability for undiluted MTA Repair were higher than control (p < 0.05). For White MTA, at 24 and 48 h, all dilutions were cytotoxic (p < 0.05). All cements led to reduced release of total TGF-β1 from the APCs (p < 0.05). In conclusion, cell viability varied depending on the material and dilution. Only Bio-C repair and MTA repair led to higher cell viability of APCs. All materials induced a decrease in the release of total TGF-β1 from the APCs.

One of the potential implementation of mesoporous silica nanomaterials (MSNs) is their use in biomedical applications as adsorbents or carriers of various bioactive substances. In this study, we attempted to fabricate silica nanomaterials containing copper and silver that were introduced into the MSN matrix, for the first time using oxalate compounds as a metal source. The syntheses were carried out using hydrothermal and impregnation methods. Structure studies revealed that the obtained nanoparticles were of a spheroidal shape and most had diameters in the range 200-500 nm. Silver and copper were found to be grouped into clusters in most samples, except in copper-decorated MSNs prepared with the impregnation method, which had an even distribution of metal atoms throughout the volume of the granule. An evaluation of the cytotoxic and irritating effects revealed that the preferred candidates for potential future applications in medicine or cosmetology among materials obtained with the presented method are the copper-conjugated MSNs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Escorting therapeutics for malignancies by nano-encapsulation to ameliorate treatment effects and mitigate side effects has been pursued in precision medicine. However, the majority of drug delivery systems suffer from uncontrollable drug release kinetics and thus lead to unsatisfactory triggered-release efficiency along with severe side effects. Herein, we developed a unique nanovesicle delivery system that shows near-infrared (NIR) light-triggered drug release behavior and minimal premature drug release. By co-encapsulation of superparamagnetic iron oxide (SPIO) nanoparticles, the ultrasound contrast agent perfluorohexane (PFH), and cisplatin in a silicate-polyaniline vesicle, we achieved the controllable release of cisplatin in a thermal-responsive manner. Specifically, vaporization of PFH triggered by the heat generated from NIR irradiation imparts high inner vesicle pressure on the nanovesicles, leading to pressure-induced nanovesicle collapse and subsequent cisplatin release. Moreover, the multimodal imaging capability can track tumor engagement of the nanovesicles and assess their therapeutic effects. Due to its precise inherent NIR-triggered drug release, our system shows excellent tumor eradication efficacy and biocompatibility in vivo , empowering it with great prospects for future clinical translation.

The magnetic MgFe 2 O 4 nanoparticles (NPs) were fabricated via a facile co-precipitation technique and was comprehensively characterized by XRD, FTIR, SEM, EDX and VSM. The prepared NPs were used as catalyst in presence of ultrasound (US) irradiation to activate persulfate (PS) for generation of sulfate radicals (SO 4 ·- ) for boosted degradation of toxic Brilliant Green (BG) dye. Preliminary experiments revealed that highest BG dye degradation efficiency of 91.63% was achieved at MgFe 2 O 4 catalyst dose of 1.0 g/L, PS dose of 300 mg/L, and initial dye concentration of 70 ppm within 15 min of US irradiation. However, only US, US in presence of PS oxidation and US in presence of MgFe 2 O 4 catalyst have shown 20.2%, 83.6% and 45.0% of BG dye removal, respectively. Furthermore, response surface methodology (RSM) based central composite design (CCD) was executed to investigate the effect of interaction between independent variables such as MgFe 2 O 4 catalyst dose (0.5-1.5 g/L), PS dose (150-350 mg/L), initial BG dye concentration (50-150 ppm) and US irradiation time (4-12 min). The RSM based quadratic model was used to predict the experimental data, and the prediction accuracy was confirmed by analysis of variance (R 2  = 0.98). The established RSM model has predicted the optimum experimental conditions as MgFe 2 O 4 catalyst dose of 0.75 g/L, PS dose of 300 mg/L, initial dye concentration of 75 ppm and sonication time of 10 min. Subsequently, the treatment cost analysis was performed for all thirty experimental runs of CCD, and the RSM predicted response was found to be evidently optimum as this has delivered best economic condition (140 $/kg of BG removed) with respect to relative dye removal (%). COD removal and residual sulfate analysis have demonstrated satisfactory reduction of COD (90.31%) as well as sulfate ions (42.87 ppm) in the dye solution after treatment. Results of degradation pathway analysis portrayed the transformation of BG molecule (M/Z ratio 385) into simpler fractions with M/Z ratio of 193, 161, 73, and 61. Moreover, the toxicity analysis revealed that sono-catalytically activated PS system has efficiently reduced the toxicity level of BG dye from 93.9% to 5.13%., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Titanium is widely utilized for manufacturing medical implants due to its inherent mechanical strength and biocompatibility. Recent studies have focused on developing coatings to impart unique properties to Ti implants, such as antimicrobial behavior, enhanced cell adhesion, and osteointegration. Ca- and Si-based ceramic (CS) coatings can enhance bone integration through the release of Ca and Si ions. However, high degradation rates of CS ceramics create a basic environment that reduces cell viability. Polymeric or protein-based coatings may be employed to modulate CS degradation. However, it is challenging to ensure coating stability over extended periods of time without compromising biocompatibility. In this study, we employed a fluorous-cured collagen shell as a drug-loadable scaffold around CS nanorod coatings on Ti implants. Fluorous-cured collagen coatings have enhanced mechanical and enzymatic stability and are able to regulate the release of Ca and Si ions. Furthermore, the collagen scaffold was loaded with antimicrobial peptides to impart antimicrobial activity while promoting cell adhesion. These multifunctional collagen coatings simultaneously regulate the degradation of CS ceramics and enhance antimicrobial activity, while maintaining biocompatibility.

This study evaluated the physicochemical, biological, and antimicrobial properties of a new hydraulic calcium silicate-based modified material, and compared it with MTA Repair HP and MTA Angelus. The materials were assessed regarding color luminosity (L), color change, radiopacity, setting time, and ISO 6876:2012 linear flow. Volumetric filling and volume change were evaluated using microcomputed-tomography (µCT). Chemical characterization after 28 days in Hank's Balanced Salt Solution (HBSS) and pH analysis were also assessed. Biological characterization of cytotoxicity and microbiological assessment were also undertaken. Shapiro-Wilk, ANOVA, Levene and post hoc analyses with Bonferroni correction were performed, adopting a 5% significance level (p <0.05). Bio-C Pulpo exhibited the highest L values after 90 days. All tested materials demonstrated color change during the analyses, and had radiopacity above 5 mm Al. MTA Repair HP set faster than Bio-C Pulpo, whereas the latter had the highest linear flow. MTA Repair HP had the highest volumetric filling in µCT analysis. Bio-C Pulpo showed the highest alkalinity during all tested periods, and the highest volumetric loss (above 9%), in comparison with MTA Repair HP and MTA Angelus. Bio-C Pulpo did not form calcium hydroxide after hydration. MTA Repair HP demonstrated the highest cytocompatibility, and Bio-C Pulpo, the highest cytotoxicity. No inhibition halos were observed for any material, and similar higher turbidity values were seen after direct contact. Composition additives used in Bio-C Pulpo modified its properties, and both the absence of calcium hydroxide deposition after hydration, and the related cytotoxicity of this material are of particular concern.

Aim: To investigate the effects of N-acetyl cysteine (NAC), Biodentine, ProRoot MTA and their combinations, on cell viability, mitochondrial reactive oxygen species (mtROS) production, mineralization and on the expression of genes related to inflammatory cytokine production, mitochondrial dynamics and cell apoptosis of lipopolysaccharide (LPS)-induced human dental pulp cells (hDPCs)., Methodology: Isolated hDPCs were exposed to 20 μg mL -1 of Escherichia coli (E. coli) LPS for 24 h, before the experiment, except for the control group. Eight experimental groups were assigned: (i) control (hDPCs cultured in regular medium), (ii) +LPS (hDPCs cultured in LPS medium throughout the experiment), (iii) -LPS/Media, (iv) -LPS/BD, (v) -LPS/MTA, (vi) -LPS/NAC, (vii) -LPS/BD + NAC and (viii) -LPS/MTA + NAC. Cell viability was measured using Alamar blue assay at 24 and 48 h. Production of mtROS was evaluated at 6 and 24 h by MitoSOX Red and MitoTracker Green. The expressions of IL-6, TNF-α, Bcl-2, Bax, Mfn-2 and Drp-1 genes were investigated at 6 h using reverse transcriptase-polymerase chain reaction (RT-PCR). For differentiation potential, cells were cultured in the osteogenic differentiation media and stained using Alizarin red assay at 14 and 21 days. The Kruskal-Wallis test, Mann-Whitney U test and one-way anova were performed for statistical analysis., Results: NAC was associated with significantly greater LPS-induced hDPC viability (P < 0.05). Both Biodentine and MTA extracts promoted cell survival, whereas the combination of NAC to these material extracts significantly increased the number of viable cells at 24 h (P < 0.05). Biodentine, MTA or NAC did not alter the mtROS level (P > 0.05). NAC supplementation to the MTA extract significantly reduced the level of IL-6 and TNF-α expression (P < 0.05). Regarding mitochondrial dynamics, the use of NAC alone promoted significant Mfn-2/Drp-1 expression (P < 0.05). Most of the groups exhibited a level of Bcl-2/Bax gene expression similar to that of the control group. The increases in mineralization productions were observed in most of the groups, except the LPS group (P < 0.05)., Conclusions: The antioxidant effect of NAC was not evident under the LPS-induced condition in DPC in vitro. NAC combined either with Biodentine or MTA improved LPS-induced hDPCs survival at 24 h. The combination of NAC with MTA promoted mineralization., (© 2021 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Biosilicate is a bioactive glass-ceramic used in medical and dental applications. This study evaluated novel reparative materials composed of pure tricalcium silicate (TCS), 30% zirconium oxide (ZrO 2 ) and 10 or 20% biosilicate, in comparison with Biodentine. Setting time was evaluated based on ISO 6876 standard, radiopacity by radiographic analysis, solubility by mass loss, and pH by using a pH meter. Cytotoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and NR assays. Alkaline phosphatase (ALP) activity and alizarin red were used to evaluate cell bioactivity. Antimicrobial activity was assessed on Enterococcus faecalis by the direct contact test. The data were submitted to analysis of variance (ANOVA)/Tukey; Bonferroni and Kruskal-Wallis, and Dunn tests (α = 0.05). The association of Biosilicate with TCS + ZrO 2 had appropriate setting time, radiopacity, and solubility, alkaline pH, and antimicrobial activity. TCS and Biodentine showed higher ALP activity in 14 days than the control (serum-free medium). All cements produced mineralized nodules. In conclusion, Biosilicate + TCS ZrO 2 decreased the setting time and increased the radiopacity in comparison to TCS. Biosilicate + TCS ZrO2 presented lower solubility and higher radiopacity than Biodentine. In addition, these experimental cements promoted antimicrobial activity and mineralization nodules formation, suggesting their potential for clinical use., (© 2020 Wiley Periodicals LLC.)

Objectives: The present study evaluated the indentation depth, storage modulus and biocompatibility of an experimental endodontic putty designed for endodontic perforation repair and direct pulp-capping (NeoPutty). The results were compared with the properties associated with the commercially available EndoSequence BC RRM Putty (ES Putty)., Methods: Indentation depth was measured by a profilometer following indentation with the 1/4 lb Gilmore needle. Elastic modulus was evaluated using a strain-controlled rheometer. The effects of eluents derived from these two putties were examined on the viability and proliferation of human dental pulp stem cells (hDPSCs) and human periodontal ligament fibroblasts (hPDLFs), before (1 st testing cycle) and after complete setting (2nd testing cycle)., Results: The ES Putty became more difficult to ident and acquired a larger storage modulus after exposure to atmospheric moisture. Biocompatibility results indicated that both putties were relatively more cytotoxic than the bioinert Teflon negative control, but much less cytotoxic than the zinc oxide-eugenol cement negative control. NeoPutty was less cytotoxic than ES putty in the 1st testing cycle, particularly with hDPSCs. Both putties exhibited more favourable cytotoxicity profiles after complete setting., Conclusions: NeoPutty has a better window of maneuverability after exposure to atmospheric moisture. From an in vitro cytotoxicity perspective, the NeoPutty may be considered more biocompatible than ES putty., Clinical Significance: The experimental NeoPutty is biocompatible and is capable of reducing the frustration of shortened shelf life when jar-stored endodontic putties are exposed to atmospheric moisture during repeated opening of the lid for clinical retrieval., (Published by Elsevier Ltd.)

Objective: This study aims to analyze the addition of niobium silicate particles to dental adhesive resins and evaluate its physicomechanical and biological properties., Methods: The SiNb particles were produced by the sol-gel route and presented a mean particle size of 2.1 μm and a specific surface area of 616,96m2/g. An experimental adhesive resin was formulated with 66 wt% Bisphenol A-Glycidyl Methacrylate and 33 wt% Hydroxyethyl methacrylate with diphenyl(2,4,6-trimethyl benzoyl)phosphine oxide as the photoinitiator. The SiNb particles were incorporated into the adhesive resins in 1 wt% (SiNb1%) and 2 wt% (SiNb2%) concentration. A control group (SiNb0%) without the addition of particles was used. The developed adhesives were evaluated by their polymerization kinetics, refractive index, softening in solvent, cytotoxicity, mineral deposition, ultimate tensile strength, and micro shear bond strength., Results: The refractive index range was increased by the addition of niobium silicate particles. No statistically significant difference was found between groups in the degree of conversion,.softening in solvent analysis, cytotoxicity and ultimate tensile strength. The deposition of minerals increased after immersion of specimens in SBF after 14 days on the SiNb2%. The SiNb2% group showed high micro shear bond strength values, reaching 33.87 MPa., Conclusion: In the present study, the addition of 2 wt% of niobium silicate into dental adhesive resins promoted the mineral deposition with increased bond strength without affecting other material properties., Clinical Significance: Bioactive fillers must maintain the physical-chemical properties of dental adhesives, guaranteeing their clinical performance. Niobium silicate particles could promote the remineralization of dentin hard tissues without compromising the physico-mechanical properties on these materials., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aim: To evaluate the in vitro effect of the novel adhesive monomer CMET, a calcium salt of 4-methacryloxyethyl trimellitate (4-MET), on the proliferation, mineralization and differentiation of odontoblast-like cells, comparing with 4-MET, calcium hydroxide (CH) and mineral trioxide aggregate (MTA)., Methodology: Rat odontoblast-like MDPC-23 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 5% foetal bovine serum. The powder of four tested materials (CMET, 4-MET, CH and MTA) was first dissolved in distilled water (dH 2 O) and then was diluted by DMEM to yield final concentrations. Solvent (dH 2 O) was used as a control. Cell viability was assessed using CCK-8 assay. Real-time RT-PCR was used to quantify the mRNA expression of odontogenic markers, cytokines and integrins. Mineralization inducing capacity was evaluated by alkaline phosphatase (ALPase) activity and alizarin red S staining. Statistical analyses were performed using one-way anova and post hoc Tukey's HSD test, with the significance level at 1%., Results: Cell viability was significantly greater in the CMET- (83 to 828 mmol L -1 ), CH- and MTA-treated (low concentrations) groups than that in the control group (P < 0.01). Higher concentrations of each material decreased the viable cells to different extents (P < 0.01). CMET treatment augmented the expression of several integrin subunits and exhibited the highest mRNA expression levels of odontogenic markers among all groups (P < 0.01). CH and MTA treatment caused significantly greater upregulation of pro-inflammatory cytokines expression than the other groups (P < 0.01). The calcific deposition of MDPC-23 cells was dose-dependently accelerated by the addition of CMET (P < 0.01); the enhancement of mineralization was also found in the fresh prepared CH and MTA treatments. Besides, CMET showed consistency in mineralization induction after 8 weeks storage. Exposure to SB202190, a specific p38 mitogen-activated protein kinases inhibitor, significantly decreased the ALPase activity as well as the mineral deposition which was enhanced by CMET treatment (P < 0.01)., Conclusions: The novel bio-active monomer had the lowest cytotoxicity among all groups and it induced the proliferation, mineralization and differentiation of odontoblast-like cells under appropriate concentrations. This adhesive monomer possesses excellent biocompatibility and hence exhibits great potential in dentine regeneration., (© 2020 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

The high reactive oxygen species (ROS) generation ability and simple construction of sonosensitizer systems remain challenging in sonodynamic therapy against the hypoxic tumor. In this work, we rationally prepared MOF-derived double-layer hollow manganese silicate nanoparticle (DHMS) with highly effective ROS yield under ultrasound irradiation for multimodal imaging-guided sonodynamic therapy (SDT). The presence of Mn in DHMS increased ROS generation efficiency because it could be oxidized by holes to improve the electron-hole separation. Moreover, DHMS could produce oxygen in the tumor microenvironment, which helps overcome the hypoxia of the solid tumor and thus enhance the treatment efficiency. In vivo experiments demonstrated efficient tumor inhibition in DHMS-mediated SDT guided by ultrasound and magnetic resonance imaging. This work presents a MOF-derived nanoparticle with sonosensitive and oxygen generating ability, which provides a promising strategy for tumor hypoxia in SDT., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recently, Mn(II)-based T 1 -weighted magnetic resonance imaging (MRI) contrast agents (CAs) have been explored widely for cancer diagnosis. However, the "always-on" properties and poor excretability of the conventional Mn(II)-based CAs leads to high background signals and unsatisfactory clearance from the body. Here, we report an " in situ three-dimensional to two-dimensional (3D-to-2D) transformation" method to prepare novel excretable 2D manganese-based layered silicates (Mn-LSNs) with extremely high signal-to-noise for tumor-specific MR imaging for the first time. Our observations combined with density functional theory (DFT) calculations reveal that 3D metal (Mn, Fe, Co) oxide nanoparticles are initially formed from the molecular precursor solution and then in situ transform into 2D metal (Mn, Fe, Co)-based layered silicates triggered by the addition of tetraethyl orthosilicate, which provides a time-saving and versatile way to prepare novel 2D silicate nanomaterials. The unique ion-exchangeable capacity and high host layer charge density endow Mn-LSNs with an "ON/OFF" pH/GSH stimuli-activatable T 1 relaxivity with superb high signal-to-noise (640-, 1200-fold for slightly acidic and reductive changes, respectively). Further in vivo MR imaging reveals that Mn-LSNs exhibit a continuously rapid T 1 -MRI signal enhancement in tumor tissue and no visible signal enhancement in normal tissue, indicating an excellent tumor-specific imaging. In addition, Mn-LSNs exhibit a rapid excretion from the mouse body in 24 h and invisible organ toxicity, which could help to solve the critical intractable degradation issue of conventional inorganic CAs. Moreover, the tumor microenvironment (pH/GSH/H 2 O 2 ) specific degradability of Mn-LSNs could help to improve the penetration depth of particles into the tumor parenchyma. Developing this novel Mn-LSNs contrast agent, together with the already demonstrated capacity of layered silicates for drug and gene delivery, provides opportunities for future cancer theranostics.

Objective: The present study assessed cytotoxicity, cell adhesion, and apoptotic gene expression in periodontal ligament fibroblasts (PLF) treated with 2 endodontic sealers., Methods: PLF cells were obtained from nonerupted third molars and cultured. MTS and LIVE/DEAD assays were performed using different treatments and time periods. Cellular adhesion was evaluated using immunocytochemistry for integrin β1 and vinculin expression, and the gene expressions of nuclear factor kB (NF-кB), P53, and apoptotic protease-activating factor 1 (Apaf-1) were evaluated using PCR., Results: Cell proliferation at 12, 24, and 48 h was statistically significant in the control and PLF groups receiving different treatments; PLF treated with culture medium containing non-hardened (NH) sealers showed a decrease in the number of cells. PLF treated with culture medium containing hardened (H) sealers also exhibited a decreased cell population. Integrin β1 and vinculin were expressed in both cell cultures treated with Acroseal (NH and H); however, the cell morphology changed and the cell population decreased. The gene expression of NF-kB and that of P53 were significantly different between the control group and the groups treated with the different sealers; mineral trioxide aggregate (MTA) (NH and H) inhibited Apaf-1, and PLF treated with Acroseal H exhibited increased Apaf-1 expression., Conclusion: Both sealers showed a certain level of cytotoxicity. The gene expression of NF-κB and P53 in PLF treated with the sealers showed significant changes compared to that of the control group, and MTA inhibited Apaf-1.

Silver nanoparticles (nAg) are often produced with different coatings that could influence bioavailability and toxicity in aquatic organisms. The purpose of this study was to examine the influence of 4 surface coatings of nAg of the same core size towards bioavailability and toxicity in juvenile rainbow trout (Oncorhynchus mykiss). Juveniles were exposed to 50 μg/L of 50 nm diameter nAg for 96 h at 15 °C with the following coatings: branched polyethylenimine (bPEI), citrate, polyvinylpyrrolidone (PVP) and silicate (Si). The data revealed that the coatings influenced hepatic Ag loadings in the following trend PVP > citrate > bPEI and Si with estimated bioavailability factors of 28, 18, 6 and 2 L/kg respectively. Hepatic Ag levels were significantly associated with DNA damage and inflammation as determined by arachidonate cyclooxygenase activity. The bPEI and citrate-coated nAg consistently produced the observed effects above in addition to increased mitochondrial electron transport activity and glutathione S-transferase activity. The absence of metallothionein and lipid peroxidation suggests that mechanisms other than the liberation of Ag + were at play. In conclusion, surface coatings were shown to significantly influence bioavailability and toxic properties of nAg to rainbow trout juveniles., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Biosoluble AES wools are increasingly used since considered not hazardous, however, few toxicity studies are available. We evaluated cytotoxic, genotoxic-oxidative and inflammatory effects of two differently soluble AES wools, AES1 (high MgO percentage) and AES2 (high CaO percentage), on alveolar (A549) and bronchial (BEAS-2B) cells. Fiber dimensions and dissolution in cell media were evaluated by SEM analysis. Cell viability, LDH release, direct/oxidative DNA damage (fpg-comet assay) and IL-6, IL-8 and TNF-α release (ELISA), were analysed after 24 h exposure to 2-200 μg/ml. On A549 cells AES1 induced LDH release, slight direct DNA damage and oxidative DNA damage with very high IL-6 release at 100 μg/ml; AES2 induced higher DNA damage than AES1 and slight oxidative DNA damage. On BEAS-2B cells we found direct DNA damage (higher for AES1) and slight oxidative DNA damage (associated to slight increased IL-6 and IL-8 release for AES1). The higher genotoxicity of more soluble AES2 on A549 cells could be explained by higher respirable fibers % and fiber number/μg found after 24 h in RPMI-medium at 100 μg/ml. The higher membrane damage, oxidative DNA damage and inflammation induced by AES1 in A549 cells could be due to the higher D LG and silica percentage. These findings suggest further investigations on AES toxicity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The purpose of this work was to evaluate the physicochemical properties, the cytotoxicity and in vivo biocompatibility of MTA Repair HP (MTA HP) and White MTA (WMTA). The setting time, flow, radiopacity and water solubility were assessed. To the cytotoxicity assay, primary human osteoblast cells were exposed to several dilutions of both materials eluates. MTT assay, apoptosis assay and cell adhesion assay were performed. The in vivo biocompatibility was evaluated through histological analysis using different staining techniques. No differences were observed between MTA HP and WMTA for setting time, radiopacity, solubility and water absorption (P > 0.05). However, MTA HP showed a significantly higher flow when compared to WMTA (P < 0.05). Cell viability results revealed that the extracts of WMTA and MTA HP promoted the viability of osteoblasts. After incubation of cells with the endodontic cement extracts, the percentage of apoptotic or necrotic cells was very low (<3%). Furthermore, SEM results showed a high degree of cell proliferation and adhesion on both groups. MTA HP showed similar in vivo biocompatibility to the WMTA and the control group in all time-points. The MTA HP presented adequate physicochemical and biological properties with improved flow ability when compared to WMTA. Such improved flow ability may be a result of the addition of a plasticizing agent and should be related to an improvement in the handling of MTA HP.

The current effort demonstrates that lutetium oxyorthosilicate doped with 1-10% cerium (Lu 2 SiO 5 :Ce, LSO:Ce) radioluminescent particles can be coated with a single dye or multiple dyes and generate an effective energy transfer between the core and dye(s) when excited via X-rays. LSO:Ce particles were surface modified with an alkyne modified naphthalimide (6-piperidin-1-yl-2-prop-2-yn-1-yl-1 H-benzo[ de]isoquinoline-1,3-(2 H)-dione, AlNap) and alkyne modified rhodamine B ( N-(6-diethylamino)-9-{2-[(prop-2-yn-1-yloxy)carbonyl]phenyl}-3 H-xanthen-3-ylidene)- N-ethylethanaminium, AlRhod) derivatives to tune the X-ray excited optical luminescence from blue to green to red using Förster Resonance Energy Transfer (FRET). As X-rays penetrate tissue much more effectively than UV/visible light, the fluorophore modified phosphors may have applications as bioimaging agents. To that end, the phosphors were incubated with rat cortical neurons and imaged after 24 h. The LSO:Ce surface modified with AlNap was able to be successfully imaged in vitro with a low-output X-ray tube. To use the LSO:Ce fluorophore modified particles as imaging agents, they must not induce cytotoxicity. Neither LSO:Ce nor LSO:Ce modified with AlNap showed any cytotoxicity toward normal human dermal fibroblast cells or mouse cortical neurons, respectively.

We analyzed the mesothelioma mortality in cohorts of workers exposed to crocidolite, amosite, and chrysotile to estimate asbestos fiber potency for mesothelioma, using the method of Hodgson and Darnton (2000). We relied on the original 17 cohort studies in their analysis, along with 3 updates of those studies and 3 new asbestos cohort studies published since 2000. We extended the analyses to examine the mesothelioma potency of tremolite in vermiculite from Libby, Montana, and for non-asbestiform elongate mineral particles (EMPs) in taconite iron ore, talc, and South Dakota gold mining. Mesothelioma potency (R Meso ) was calculated as the percent of all expected deaths that were due to mesothelioma per fiber/cc-year of exposure.The R Meso was 0.0012 for chrysotile, 0.099 for amosite, and 0.451 for crocidolite: thus, the relative potency of chrysotile:amosite:crocidolite was 1:83:376, which was not appreciably different from the estimates by Hodgson and Darnton in 2000. The R Meso for taconite mining fibers was 0.069 which was slightly smaller than that for amosite. The R Meso for Libby fibers was 0.028 which was greater than that for chrysotile and less than that for amosite. Talc and gold mining EMPs were non-potent for mesothelioma. Although there are a number of methods for estimating fiber potency of asbestos and non-asbestiform EMPs, the method of Hodgson and Darnton provides a uniform method by which fiber potency can be compared across many fiber types. Our estimates of R Meso provide a useful addition to our knowledge of mesothelioma potency for different asbestos and non-asbestiform EMP fibers., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The investigation of the biocompatibility of potential and commercially available dental material is a major challenge in dental science. This study demonstrates that the zebrafish model is a novel in vivo model for investigating the biocompatibility of dental materials. Two commercially available dental materials, mineral trioxide aggregate (MTA) and Biodentine, were assessed for their biocompatibility. The biocompatibility analysis was performed in embryonic zebrafish with the help of standard toxicity assays measuring essential parameters such as survivability and hatching. The mechanistic and comparative analysis of toxicity was performed by oxidative stress analysis by measuring ROS induction and apoptosis in zebrafish exposed to dental materials at different concentrations. The molecular investigation at the protein level was done by a computational approach using in silico molecular docking and pathway analysis. The toxicity analysis showed a significant reduction in hatching and survivability rates along with morphological malformations with an increase in the concentration of exposed materials. ROS and apoptosis assay results revealed a greater biocompatibility of Biodentine as compared to that of MTA which was concentration-dependent. In silico analysis showed the significant role of the tricalcium silicate-protein ( Sod1, tp53, RUNX2B) interaction in an exhibition of toxicity. The study provides a new vision and standard in dental material sciences for assessing the biocompatibility of potential novel and commercially available dental materials.

Aim: To evaluate and compare the cytotoxic effects of different types of root canal., Materials and Methods: The sealers were eluted with culture medium for 1 hour, 7 days, and 14 days. Cell viability was estimated by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and trypan blue exclusion method on human periodontal ligament (PDL) fibroblast cells. Sealers used are mineral trioxide aggregate (MTA)-based sealer (MTA Fillapex, Angelus), calcium hydroxide-based sealer (Apexit Plus, Ivoclar Vivadent), resin-based sealer (AH Plus, Dentsply), and zinc oxide eugenol-based sealer (Tubli Seal, SybronEndo)., Results: The order of cytotoxicity through MTT assay, at the end of the second week, was observed as MTA Fillapex> Tubli Seal> Apexit Plus > AH Plus. The percentage cell viability obtained after trypan blue exclusion method decreased in the order of Apexit Plus> Tubli Seal> AH Plus> MTA Fillapex, which was similar to the reported cytotoxicity from the MTT assay after 1 hour., Conclusion: Each type of sealer showed moderate-to-severe cytotoxic response when compared with the control. The MTA Fillapex was found to be the most cytotoxic sealer. Use of resin-based material as a root canal sealer may result in a more favorable response to PDL fibroblasts., Clinical Significance: Having knowledge of the cytotoxicity of various sealers will help in increasing patient's comfort.

Aim: The purpose of this study was to evaluate and compare the cytotoxicity and genotoxicity of two bioceramic root canal sealers: EndoSequence BC and iRoot SP with zinc oxide eugenol sealers on fibroblast cell line., Materials and Methods: The sealers tested were zinc oxide eugenol, EndoSequence BC, and iRoot SP. Each material was mixed according to the manufacturer's instructions and mounted into sterile polyethylene color-coded rings, for cytotoxicity and genotoxicity evaluation. After 48 hours, the set materials were transferred to previously marked wells and cytotoxicity evaluation to L929 murine fibroblast cells was done by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The percentages of viable cells were then calculated and values were statistically analyzed by Kruskal-Wallis test. The evaluation of genotoxicity of the materials to L929 murine fibroblast cells was carried out by Comet assay. To quantify deoxyribonucleic acid (DNA) damage, the following comet parameters were evaluated in the assay using Comet scoring software: tail length, tail moment, and Olive moment. The values were statistically analyzed using Kruskal-Wallis test with a significance value set to p < 0.05., Results: The results of the study showed that both cytotoxicity and genotoxicity evaluation by MTT assay and Comet assay can be done on L929 murine fibroblast cell line. Among the three tested materials, zinc oxide eugenol showed maximum cytotoxicity to the cells (30.64% viable cells), followed by EndoSequence BC (71.33% viable cells) and iRoot SP (75.11% viable cells). The evaluation of DNA damage by genotoxicity assessment showed iRoot SP to be least genotoxic followed closely by EndoSequence BC. Zinc oxide eugenol was genotoxic and induced more DNA damage on the fibroblast cell line studied. The statistical analyses for both the assays were nonsignificant., Conclusion: All the three tested sealers showed varying degrees of cytotoxicity and genotoxicity while using fibro-blast cell line. Zinc oxide eugenol was most toxic in both the assays and iRoot SP showed least toxicity, followed closely by EndoSequence BC.

High-Temperature Insulation Wools (HTIW), such as alumino silicate wools (Refractory Ceramic Fibers) and Alkaline Earth Silicate wools, are used in high-temperature industries for thermal insulation. These materials have an amorphous glass-like structure. In some applications, exposure to high temperatures causes devitrification resulting in the formation of crystalline species including crystalline silica. The formation of this potentially carcinogenic material raises safety concerns regarding after-use handling and disposal. This study aims to determine whether cristobalite formed in HTIW is bioactive in vitro. Mouse macrophage (J774A.1) and human alveolar epithelial (A549) cell lines were exposed to pristine HTIW of different compositions, and corresponding heat-treated samples. Cell death, cytokine release, and reactive oxygen species (ROS) formation were assessed in both cell types. Cell responses to aluminum lactate-coated fibers were assessed to determine if responses were caused by crystalline silica. DQ12 α-quartz was used as positive control, and TiO 2 as negative control. HTIW did not induce cell death or intracellular ROS, and their ability to induce pro-inflammatory mediator release was low. In contrast, DQ12 induced cytotoxicity, a strong pro-inflammatory response and ROS generation. The modest pro-inflammatory mediator responses of HTIW did not always coincide with the formation of cristobalite in heated fibers; therefore, we cannot confirm that devitrification of HTIW results in bioactive cristobalite in vitro. In conclusion, the biological responses to HTIW observed were not attributable to a single physicochemical characteristic; instead, a combination of physicochemical characteristics (cristobalite content, fiber chemistry, dimensions and material solubility) appear to contribute to induction of cellular responses.

Background: Mineral trioxide aggregate (MTA) is widely used for pulp-capping procedures in permanent teeth and as a gold standard material in endodontics. The aim of the study was to investigate the effect of MTA on cell viability and apoptosis when MTA is directly in contact with Stem Cells from Human Exfoliated Deciduous Teeth (SHEDs)., Methods: MTA was mixed and coated in the bottom of a 24-well plate. SHEDs collected and cultured from normal exfoliated human deciduous teeth (passages 3-4) were seeded on square cover glasses. The glasses with seeded SHEDs were incubated in the plates with or without MTA coating. They were divided into four groups: MTA direct contact, direct control, MTA indirect contact, and indirect control. After 1, 2 and 3 days of culturing, cell morphology was observed and cell viability was assessed by the WST-1 cell cytotoxicity assay. TUNEL assay, immunofluorescent labeling and western blot analysis were used to study the effects of MTA on SHEDs apoptosis., Results: MTA impaired cell viability of SHEDs in 1, 2 and 3 days, and the effect of direct contact was more severe. Cell apoptosis with positive Annexin V and TUNEL staining was noted when there was direct contact with MTA. Western blot analysis revealed that Bcl-2 and Bcl-xL decreased after SHEDs were in contact with MTA., Conclusions: This study shows that direct contact with 1 week post-set MTA significantly decreases the viability of SHEDs and induced cell apoptosis. The results suggest that there is a possible cytotoxic effect of pulp tissue when there is direct contact with MTA. Different responses would be expected due to the strong alkaline characteristics of fresh mixed MTA.

Proinflammatory responses are important aspects of the immune response to biomaterials, which may cause peri-implantitis and implant shedding. The purpose of this study was to test the cytotoxicity and proinflammatory effects of dicalcium silicate particles on RAW 264.7 macrophages and to investigate the proinflammatory response mechanism induced by C 2 S and tricalcium phosphate (TCP). C 2 S and TCP particles were characterized using scanning electron microscopy (SEM), energy spectrum analysis (EDS) and X-ray diffraction (XRD). Cytotoxicity and apoptosis assays with C 2 S and TCP in the murine RAW 264.7 cell line were tested using the cell counting kit-8 (CCK-8) assay and flow cytometry (FCM). The detection results showed that C 2 S and TCP particles had no obvious toxicity in RAW 264.7 cells and did not cause obvious apoptosis, although they both caused an oxidative stress response by producing ROS when the concentrations were at 100  μ g/mL. C 2 S particles are likely to induce a proinflammatory response by inducing high TLR2, TNF- α mRNA, TNF- α proinflammatory cytokine, p-I κ B, and p-JNK1 + JNK2 + JNK3 expression levels. When we added siRNA-TLR2-1, a significant reduction was observed. These findings support the theory that C 2 S particles induce proinflammatory responses through the TLR2-mediated NF- κ B and JNK pathways in the murine RAW 264.7 macrophage cell line.

Introduction: Resin sealers with biocompatible and bioactive additives have been used in clinical practice. Recently, a calcium silicate root canal sealer was introduced under the name BioRoot RCS (Septodont, Saint Maur-des-Fossés, France). The aim of this study was to evaluate the effects of BioRoot RCS on cell survival and proliferation of cultured cells in parallel with an epoxy resin sealer with calcium phosphate and calcium oxide and a salicylate resin sealer with mineral trioxide aggregate filler. The tested hypothesis was that BioRoot RCS is significantly less cytotoxic than the other tested sealers., Methods: The experiments were performed on NIH/3T3 cells (American Type Culture Collection, Manassas, VA) grown as monolayer cultures at 37°C in atmosphere containing 5% CO 2 in air and 100% relative humidity. The sealers' extracts (24 hours and 1 week) were applied to cells at 1:1 and 1:2 dilutions. The effect was assessed by a modified sulforhodamine B staining assay in reference to controls after 24 and 72 hours of exposure. All experiments were performed at least twice in 6 replicates. Analysis of variance and post hoc comparison tests were used to evaluate the statistical significance of the results at a level of significance of P = .05., Results: BioRoot RCS was significantly less cytotoxic than the other 2 sealers. MTA-Fillapex (Angelus, Londrina, Brazil) and SimpliSeal (Discuss Dental, LLC, Calver City, CA) exhibited a similar antiproliferative profile with no statistically significant differences in all settings., Conclusions: BioRoot RCS showed quite a positive biological behavior. Further investigation is needed in order to clarify the mechanism and the components that contribute to the beneficial results observed., (Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Laboratory desorption behaviour, function and elemental composition of commercially marketed silicate minerals used to sequester phosphorus pollution as well as Zeolite, Smectite, and Kaolinite were determined to see whether their use by environmental scientists and water managers in eutrophic waterways has the potential to contribute to longer-term environmental impacts. As expected, lower phosphorus concentrations were observed, following treatment. However, data relating to desorption, environmental fate and bioavailability of phospho-silicate complexes (especially those containing rare earth elements) appear to be underrepresented in product testing and trial publications. Analysis of desorption of phosphate (P) was > 5 μg[P]/L for all three non-commercial samples and 0 > μg[P]/L > 5 for all commercial silicates for a range of concentrations from 0 to 300 μg[P]/L. Based on a review of bioaccumulation data specific to the endangered Cherax tenuimanus (Hairy Marron) and other endemic species, this is significant considering anything > 20 μg[La]/L is potentially lethal to the hairy marron, other crustaceans and even other phyla. Where prokaryotic and eukaryotic effects are underreported, this represents a significant challenge. Especially where product protocols recommend continual reapplication, this is significant because both the forward and reverse reactions are equally important. The users of silicate minerals in water columns should accept the dynamic nature of the process and pay equal attention to both adsorption and desorption because desorption behaviour is an inherent trait. Even if broader desorption experimentation is difficult, expensive and time-consuming, it is a critical consideration nonetheless.

Background: Exposure to mineral fibers is of substantial relevance to human health. A key event in exposure is the interaction with inflammatory cells and the subsequent generation of pro-inflammatory factors. Mast cells (MCs) have been shown to interact with titanium oxide (TiO₂) and asbestos fibers. In this study, we compared the response of rat peritoneal MCs challenged with the asbestos crocidolite and nanowires of TiO₂ to that induced by wollastonite employed as a control fiber., Methods: Rat peritoneal MCs (RPMCs), isolated from peritoneal lavage, were incubated in the presence of mineral fibers. The quantities of secreted enzymes were evaluated together with the activity of fiber-associated enzymes. The ultrastructural morphology of fiber-interacting RPMCs was analyzed with electron microscopy., Results: Asbestos and TiO₂ stimulate MC secretion. Secreted enzymes bind to fibers and exhibit higher activity. TiO₂ and wollastonite bind and improve enzyme activity, but to a lesser degree than crocidolite., Conclusions: (1) Mineral fibers are able to stimulate the mast cell secretory process by both active (during membrane interaction) and/or passive (during membrane penetration) interaction; (2) fibers can be found to be associated with secreted enzymes-this process appears to create long-lasting pro-inflammatory environments and may represent the active contribution of MCs in maintaining the inflammatory process; (3) MCs and their enzymes should be considered as a therapeutic target in the pathogenesis of asbestos-induced lung inflammation; and (4) MCs can contribute to the inflammatory effect associated with selected engineered nanomaterials, such as TiO₂ nanoparticles., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Humans exposed to asbestos and/or asbestiform fibers are at high risk of developing many lung diseases including asbestosis, lung cancer, and malignant mesothelioma. However, the disease-causing potential and specific metabolic mechanisms and pathways associated with various asbestos/asbestiform fiber exposures triggering different carcinogenic and non-carcinogenic outcomes are still largely unknown. The aim of this this study was to investigate gene expression profiles and inflammatory responses to different asbestos/asbestiform fibers at the acute/sub-acute phase that may be related to delayed pathological outcomes observed at later time points. Mice were exposed to asbestos (crocidolite, tremolite asbestos), asbestiform fibers (erionite), and a low pathogenicity mineral fiber (wollastonite) using oropharyngeal aspiration. Similarities in inflammatory and tissue damage responses, albeit with quantitative differences, were observed at day 1 and 7 post treatment. Exposure to different fibers induced significant changes in regulation and release of a number of inflammatory cytokines/chemokines. Comparative analysis of changes in gene regulation in the lung on day 7 post exposure were interpretable in the context of differential biological responses that were consistent with histopathological findings at days 7 and 56 post treatment. Our results noted differences in the magnitudes of pulmonary responses and gene regulation consistent with pathological alterations induced by exposures to four asbestos/asbestiform fibers examined. Further comparative mechanistic studies linking early responses with the long-term endpoints may be instrumental to understanding triggering mechanisms underlying pulmonary carcinogenesis, that is lung cancer versus mesothelioma.

Introduction: Numerous studies reported dentin bridge formation after pulp capping with tricalcium silicates. By contrast, pulp capping with resins leads to pulp toxicity and inflammation. Hybrid materials made up of tricalcium silicates and resins have also been developed to be used in direct pulp capping. This work was designed to study the consequences of adding resins to tricalcium silicates by investigating TheraCal (BISCO, Lançon De Provence, France) and Biodentine (Septodont, Saint Maur des Fosses, France) interactions with the dental pulp., Methods: Media conditioned with the biomaterials were used to analyze pulp fibroblast proliferation using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) test and proinflammatory cytokine interleukin 8 (IL-8) secretion using the enzyme-linked immunosorbent assay. The effects of conditioned media on dentin sialoprotein (DSP) and nestin expression by dental pulp stem cells (DPSCs) were investigated by immunofluorescence. The materials' interactions with the vital pulp were investigated using the entire tooth culture model., Results: TheraCal-conditioned media significantly decreased pulp fibroblast proliferation, whereas no effect was observed with Biodentine. When DPSCs were cultured with Biodentine-conditioned media, immunofluorescence showed an increased expression of DSP and nestin. This expression was lower with TheraCal, which significantly induced proinflammatory IL-8 release both in cultured fibroblasts and entire tooth cultures. This IL-8 secretion increase was not observed with Biodentine. Entire tooth culture histology showed a higher mineralization with Biodentine, whereas significant tissue disorganization was observed with TheraCal., Conclusions: Within the limits of these preclinical results, resin-containing TheraCal cannot be recommended for direct pulp capping., (Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Aims: To investigate the cytotoxicity and bioactivity of several pulpotomy materials: Biodentine (Septodont, Saint-Maur-des-Fosses, France) MTA (Angelus, Londrina, PR, Brazil), Theracal LC (Bisco Inc., Schamburg, IL, USA) and IRM (Dentsply DeTrey GmbH, Konstanz, Germany), after contact with stem cells isolated from human exfoliated primary teeth (SHEDs)., Methodology: SHEDs were cultured in the presence of the eluates of various pulpotomy materials for 24, 48 and 72 h. Cell viability was determined by mitochondrial dehydrogenase enzymatic (MTT) assay. Apoptosis and changes in cell phenotype were evaluated by flow cytometry. Also, an in vitro scratch wound-healing assay was used to determine their effects on cell migration. To assess cell morphology and attachment to the different pulpotomy materials, SHEDs were directly seeded onto the material surfaces and analysed by scanning electron microscopy (SEM). Finally, the deposition of a calcified matrix in presence of these materials was verified by Alizarin Red staining. Statistical analysis was performed with analysis of variance and Bonferroni or Tukey post-test (α = 0.05)., Results: Cell viability in the presence of Biodentine eluates was significantly higher to that obtained using complete medium alone (control; P < 0.01) and was also significantly higher than using MTA Angelus from 48 h of incubation (P < 0.01). However, Theracal LC and IRM were associated with low rates of cell viability (P < 0.001). Similar results were obtained in an apoptosis assay. In addition, SHEDs maintained their mesenchymal phenotype in all conditions although their capacity to migrate was higher in the presence of Biodentine. SEM studies revealed a suitable proliferation rate, cell spreading and attachment, especially when using Biodentine and MTA Angelus discs. Finally, Biodentine eluates significantly induced calcified matrix deposition from 7 days of culture (P < 0.01)., Conclusions: Biodentine exhibited better cytocompatibility and bioactivity than MTA Angelus, Theracal LC and IRM., (© 2017 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

The present study was to investigate the alteration of biochemical and hematological parameters on the rats exposed to natural radiation caused by britholite mineral (REE, Ca, Na) 5 [(Si,P)O 4 ] 3 (OH,F) within 15 days. Britholite was collected from Kuluncak mining area, Malatya, bearing radioactive 232 Th isotope (average 2.68% ThO 2 ), which is rare earth elements found high amounts. Britholite is toxic for the living animal and human and emits the radiation to natural surroundings about 0.8R/h due to its radioactive 232 Th properties. In this study, animals were divided to two groups, one groups exposed to 232 Th, the other group was served as control group. All animals were fed with same food and water during the experimental study (15 days). After 15 days, the hematologic and biochemical parameters (Na, K, Ca, P, Cl, Mg, glucose, cholesterol, HDL, LDL, albumin, Uric acid, AST, ALT, total protein, Fe, urea and creatine level and hormonal parameters (TSH, T3 and T4)) were analyzed The levels of serum triglyceride in the ionizing radiation group generated by 232 Th isotope (p < 0.05) statistically significantly increased compared with control group value. Lymphocytes, TSH, T3 and T4 decreased in the ionizing radiation group generated by 232 Th isotope while neutrophils increased in the ionizing radiation group generated by 232 Th isotope. The rats exposed to ionizing radiation generated by 232 Th isotope caused significant changes in the hematological and biochemical parameters and the most significantly alteration was observed in the thyroid hormonal levels, which might be due to high radiation doses within short time. These results should be kept in mind to maintain healthy life in people who lives in britholite mineral vicinity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Mineral trioxide aggregate (MTA) is a calcium silicate dental cement used for various applications in dentistry. This study was undertaken to test whether the presence of three commercial brands of calcium silicate dental cements in the dental extraction socket of rats would affect the brain aluminium (Al) levels and oxidative stress parameters. Right upper incisor was extracted and polyethylene tubes filled with MTA Angelus, MTA Fillapex or Theracal LC, or left empty for the control group, were inserted into the extraction socket. Rats were killed 7, 30 or 60 days after operation. Brain tissues were obtained before killing. Al levels were measured by atomic absorption spectrometry. Thiobarbituric acid reactive substances (TBARS) levels, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were determined using spectrophotometry. A transient peak was observed in brain Al level of MTA Angelus group on day 7, while MTA Fillapex and Theracal LC groups reached highest brain Al level on day 60. Brain TBARS level, CAT, SOD and GPx activities transiently increased on day 7 and then returned to almost normal levels. This in vivo study for the first time indicated that initial washout may have occurred in MTA Angelus, while element leaching after the setting is complete may have taken place for MTA Fillapex and Theracal LC. Moreover, oxidative stress was induced and antioxidant enzymes were transiently upregulated. Further studies to search for oxidative neuronal damage should be done to completely understand the possible toxic effects of calcium silicate cements on the brain.