Effect of Modified Bioceramic Mineral Trioxide Aggregate Cement with Mesoporous Nanoparticles on Human Gingival Fibroblasts.

The ion doping of mesoporous silica nanoparticles (MSNs) has played an important role in revolutionizing several materials applied in medicine and dentistry by enhancing their antibacterial and regenerative properties. Mineral trioxide aggregate (MTA) is a dental material widely used in vital pulp therapies with high success rates. The aim of this study was to investigate the effect of the modification of MTA with cerium (Ce)- or calcium (Ca)-doped MSNs on the biological behavior of human gingival fibroblasts (hGFs). MSNs were synthesized via sol-gel, doped with Ce and Ca ions, and mixed with MTA at three ratios each. Powder specimens were characterized using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Biocompatibility was evaluated using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay following hGFs' incubation in serial dilutions of material eluates. Antioxidant status was evaluated using Cayman's antioxidant assay after incubating hGFs with material disc specimens, and cell attachment following dehydration fixation was observed through SEM. Material characterization confirmed the presence of mesoporous structures. Biological behavior and antioxidant capacity were enhanced in all cases with a statistically significant increase in CeMTA 50.50. The application of modified MTA with cerium-doped MSNs offers a promising strategy for vital pulp therapies.

Effect of silica-based mesoporous nanomaterials on human blood cells.

Different mesoporous nanomaterials (MSNs) are constantly being developed for a range of therapeutic purposes, but they invariably interact with blood components and may cause hazardous side effects. Therefore, when designing and developing nanoparticles for biomedical applications, hemocompatibility should be one of the primary goals to assess their toxicity at the cellular level of all blood components. The aim of this study was to evaluate the compatibility of human blood cells (erythrocytes, platelets, and leukocytes) after exposure to silica-based mesoporous nanomaterials that had been manufactured using the sol-gel method, with Ca and Ce as doping elements. The viability of lymphocytes and monocytes was unaffected by the presence of MSNs at any concentration. However, it was found that all nanomaterials, at all concentrations, reduced the viability of granulocytes. P-selectin expression of all MSNs at all concentrations was statistically significantly higher in platelet incubation on the first day of storage (day 1) compared to the control. When incubated with MSNs, preserved platelets displayed higher levels of iROS at all MSNs types and concentrations examined. Ce-containing MSNs presented a slightly better hemocompatibility, although it was also dose dependent. Further research is required to determine how the unique characteristics of MSNs may affect various blood components in order to design safe and effective MSNs for various biomedical applications.

Study of Biological Behavior and Antimicrobial Properties of Cerium Oxide Nanoparticles.

(1) Background: An element that has gained much attention in industrial and biomedical fields is Cerium (Ce). CeO2 nanoparticles have been proven to be promising regarding their different biomedical applications for the control of infection and inflammation. The aim of the present study was to investigate the biological properties and antimicrobial behavior of cerium oxide (CeO2) nanoparticles (NPs). (2) Methods: The investigation of the NPs' biocompatibility with human periodontal ligament cells (hPDLCs) was evaluated via the MTT assay. Measurement of alkaline phosphatase (ALP) levels and alizarine red staining (ARS) were used as markers in the investigation of CeO2 NPs' capacity to induce the osteogenic differentiation of hPDLCs. Induced inflammatory stress conditions were applied to hPDLCs with H2O2 to estimate the influence of CeO2 NPs on the viability of cells under these conditions, as well as to reveal any ROS scavenging properties. Total antioxidant capacity (TAC) of cell lysates with NPs was also investigated. Finally, the macro broth dilution method was the method of choice for checking the antibacterial capacity of CeO2 against the anaerobic pathogens Porphyromonas gingivalis and Prevotella intermedia. (3) Results: Cell viability assay indicated that hPDLCs increase their proliferation rate in a time-dependent manner in the presence of CeO2 NPs. ALP and ARS measurements showed that CeO2 NPs can promote the osteogenic differentiation of hPDLCs. In addition, the MTT assay and ROS determination demonstrated some interesting results concerning the viability of cells under oxidative stress conditions and, respectively, the capability of NPs to decrease free radical levels over the course of time. Antimicrobial toxicity was observed mainly against P. gingivalis. (4) Conclusions: CeO2 NPs could provide an excellent choice for use in clinical practices as they could prohibit bacterial proliferation and control inflammatory conditions.

Composite PLGA-Nanobioceramic Coating on Moxifloxacin-Loaded Akermanite 3D Porous Scaffolds for Bone Tissue Regeneration.

Silica-based ceramics doped with calcium and magnesium have been proposed as suitable materials for scaffold fabrication. Akermanite (Ca2MgSi2O7) has attracted interest for bone regeneration due to its controllable biodegradation rate, improved mechanical properties, and high apatite-forming ability. Despite the profound advantages, ceramic scaffolds provide weak fracture resistance. The use of synthetic biopolymers such as poly(lactic-co-glycolic acid) (PLGA) as coating materials improves the mechanical performance of ceramic scaffolds and tailors their degradation rate. Moxifloxacin (MOX) is an antibiotic with antimicrobial activity against numerous aerobic and anaerobic bacteria. In this study, silica-based nanoparticles (NPs) enriched with calcium and magnesium, as well as copper and strontium ions that induce angiogenesis and osteogenesis, respectively, were incorporated into the PLGA coating. The aim was to produce composite akermanite/PLGA/NPs/MOX-loaded scaffolds through the foam replica technique combined with the sol-gel method to improve the overall effectiveness towards bone regeneration. The structural and physicochemical characterizations were evaluated. Their mechanical properties, apatite forming ability, degradation, pharmacokinetics, and hemocompatibility were also investigated. The addition of NPs improved the compressive strength, hemocompatibility, and in vitro degradation of the composite scaffolds, resulting in them keeping a 3D porous structure and a more prolonged release profile of MOX that makes them promising for bone regeneration applications.

Artemisinin Loaded Cerium-Doped Nanopowders Improved In Vitro the Biomineralization in Human Periodontal Ligament Cells.

BACKGROUND: A promising strategy to enhance bone regeneration is the use of bioactive materials doped with metallic ions with therapeutic effects and their combination with active substances and/or drugs. The aim of the present study was to investigate the osteogenic capacity of human periodontal ligament cells (hPDLCs) in culture with artemisinin (ART)-loaded Ce-doped calcium silicate nanopowders (NPs); Methods: Mesoporous silica, calcium-doped and calcium/cerium-doped silicate NPs were synthesized via a surfactant-assisted cooperative self-assembly process. Human periodontal ligament cells (hPDLCs) were isolated and tested for their osteogenic differentiation in the presence of ART-loaded and unloaded NPs through alkaline phosphatase (ALP) activity and Alizarine red S staining, while their antioxidant capacity was also evaluated; Results: ART promoted further the osteogenic differentiation of hPDLCs in the presence of Ce-doped NPs. Higher amounts of Ce in the ART-loaded NPs inversely affected the mineral deposition process by the hPDLCs. ART and Ce in the NPs have a synergistic role controlling the redox status and reducing ROS production from the hPDLCs; Conclusions: By monitoring the Ce amount and ART concentration, mesoporous NPs with optimum properties can be developed towards bone tissue regeneration demonstrating also potential application in periodontal tissue regeneration strategies.

Poly(Glycerol Succinate) as Coating Material for 1393 Bioactive Glass Porous Scaffolds for Tissue Engineering Applications.

BACKGROUND: Aliphatic polyesters are widely used for biomedical, pharmaceutical and environmental applications due to their high biodegradability and cost-effective production. Recently, star and hyperbranched polyesters based on glycerol and ω-carboxy fatty diacids have gained considerable interest. Succinic acid and bio-based diacids similar to glycerol are regarded as safe materials according to the US Food and Drug Administration (FDA). Bioactive glass scaffolds utilized in bone tissue engineering are relatively brittle materials. However, their mechanical properties can be improved by using polymer coatings that can further control their degradation rate, tailor their biocompatibility and enhance their performance. The purpose of this study is to explore a new biopolyester poly(glycerol succinate) (PGSuc) reinforced with mesoporous bioactive nanoparticles (MSNs) as a novel coating material to produce hybrid scaffolds for bone tissue engineering. METHODS: Bioactive glass scaffolds were coated with neat PGSuc, PGSuc loaded with dexamethasone sodium phosphate (DexSP) and PGSuc loaded with DexSP-laden MSNs. The physicochemical, mechanical and biological properties of the scaffolds were also evaluated. RESULTS: Preliminary data are provided showing that polymer coatings with and without MSNs improved the physicochemical properties of the 1393 bioactive glass scaffolds and increased the ALP activity and alizarin red staining, suggesting osteogenic differentiation potential when cultured with adipose-derived mesenchymal stem cells. CONCLUSIONS: PGSuc with incorporated MSNs coated onto 1393 bioactive glass scaffolds could be promising candidates in bone tissue engineering applications.

SBA-15 Mesoporous Silica as Delivery Vehicle for rhBMP-2 Bone Morphogenic Protein for Dental Applications.

(1) Background: A proposed approach to promote periodontal tissue regeneration in cases of peri-implantitis is the local administration of growth factors at the implant site. Recombinant human bone morphogenetic protein-2 (rh-BMP-2) can effectively promote bone regeneration and osseointegration and the development of appropriate carriers for its delivery is of paramount importance. The aim of the present study was to develop SBA-15 mesoporous nanoparticles (MSNs) with varying porosity, evaluate their biocompatibility with human Periodontal Ligament Cells (hPDLCs) and to investigate their effectiveness as carriers of rh-BMP-2. (2) Methods: SBA-15 type mesoporous silicas were synthesized via sol-gel reaction. The calcined SBA-15 samples were characterized by N2 porosimetry, Fourier transform-infrared spectrometry (FTIR), Scanning (SEM) and Transmission Electron Microscopy (TEM). Rh-BMP-2 loading and release kinetics were evaluated by UV spectroscopy. (3) Results: MSNs presented hexagonally arranged, tubular pores of varying length and diameter. Slightly higher loading capacity was achieved for SBA-15 with large pores that presented good hemocompatibility. MTT assay revealed no cytotoxic effects for all the tested materials, while SBA-15 with large pores induced a significant upregulation of cell viability at day 5. (4) Conclusions: SBA-15 MSNs may prove a valuable delivery platform towards the effective release of bone-inducing proteins.

Electrospun PLGA Membranes with Incorporated Moxifloxacin-Loaded Silica-Based Mesoporous Nanocarriers for Periodontal Regeneration.

Engineered electrospun membranes have emerged as promising materials in guided tissue regeneration, as they provide an appropriate framework for the formation of new functional periodontal tissues. The development of multifunctional local drug delivery systems with sustained release of drugs for prolonged infection control can be used in periodontal surgical interventions to simultaneously prohibit epithelium downgrowth and ensure proper healing and regeneration of damaged periodontal tissues. The aim of the present study was the fabrication of novel composite membranes from PLGA/moxifloxacin-loaded mesoporous nanocarriers through electrospinning and the evaluation of their drug release profiles. The addition of moxifloxacin-loaded mesoporous nanocarriers in PLGA yielded a sustained and prolonged drug release, while maintaining satisfactory mechanical strength. The freshly fabricated membranes were found to be biocompatible at masses less than 1 mg after exposure to healthy erythrocytes. Increase in the amount of polymer led to more uniform fibers with large diameters and pores. The study of the parameters of the electrospinning process indicated that increase in the applied voltage value and rotation speed of the collector led to more uniform fibers with higher diameter and larger pores, suitable for tissue regeneration applications, such as periodontal tissue regeneration.

Sol-Gel Synthesis and Characterization of YSZ Nanofillers for Dental Cements at Different Temperatures.

BACKGROUND: Yttria-stabilized zirconia nanoparticles can be applied as fillers to improve the mechanical and antibacterial properties of luting cement. The aim of this study was to synthesize yttria-stabilized zirconia nanoparticles by the sol-gel method and to investigate their composition, structure, morphology and biological properties. METHODS: Nanopowders of ZrO2 7 wt% Y2O3 (nY-ZrO) were synthesized by the sol-gel method and were sintered at three different temperatures: 800, 1000 and 1200 °C, and their composition, size and morphology were investigated. The biocompatibility was investigated with human gingival fibroblasts (hGFs), while reactive oxygen species (ROS) production was evaluated through fluorescence analysis. RESULTS: All synthesized materials were composed of tetragonal zirconia, while nanopowders sintered at 800 °C and 1000 °C additionally contained 5 and 20 wt% of the cubic phase. By increasing the calcination temperature, the crystalline size of the nanoparticles increased from 12.1 nm for nY-ZrO800 to 47.2 nm for nY-ZrO1200. Nano-sized particles with good dispersion and low agglomeration were received. Cell culture studies with human gingival fibroblasts verified the nanopowders' biocompatibility and their ROS scavenging activity. CONCLUSIONS: the obtained sol-gel derived nanopowders showed suitable properties to be potentially used as nanofillers for dental luting cement.

Effect of Silica Based Nanoparticles against Plasmodium falciparum and Leishmania infantum parasites.

Malaria and Leishmaniasis are two major parasitic diseases, endemic in large areas of tropical countries with high morbidity and mortality across the world. Nanoparticles in small sizes are specifically considered in medicine due to their ability to enter the cells, control the distribution of the administered drug and carry the drug specifically to the place of action. The present study aims to introduce the application of silica nanoparticles as new promising nanotools in malaria and leishmaniasis treatment. Ion doped silica nanomaterials revealed antileishmanial activities indicating the positive role of calcium, magnesium and copper to the surface of the particles against Leishmania parasites. Artemisinin-loaded nanoparticles presented the most promising antiparasitic properties with a sustained release able to overcome the parasite invasion. The sustainable release of artemisinin guarantee both the maintenance of its potential efficacy and also introduce an administration of drug to avoid subsequent drug resistance.

Effect of Artemisinin-Loaded Mesoporous Cerium-Doped Calcium Silicate Nanopowder on Cell Proliferation of Human Periodontal Ligament Fibroblasts.

Ion doping has rendered mesoporous structures important materials in the field of tissue engineering, as apart from drug carriers, they can additionally serve as regenerative materials. The purpose of the present study was the synthesis, characterization and evaluation of the effect of artemisinin (ART)-loaded cerium-doped mesoporous calcium silicate nanopowders (NPs) on the hemocompatibility and cell proliferation of human periodontal ligament fibroblasts (hPDLFs). Mesoporous NPs were synthesized in a basic environment via a surfactant assisted cooperative self-assembly process and were characterized using Scanning Electron Microscopy (SEM), X-ray Fluorescence Spectroscopy (XRF), Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Diffraction Analysis (XRD) and N2 Porosimetry. The loading capacity of NPs was evaluated using Ultrahigh Performance Liquid Chromatography/High resolution Mass Spectrometry (UHPLC/HRMS). Their biocompatibility was evaluated with the MTT assay, and the analysis of reactive oxygen species was performed using the cell-permeable ROS-sensitive probe 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA). The synthesized NPs presented a mesoporous structure with a surface area ranging from 1312 m2/g for undoped silica to 495 m2/g for the Ce-doped NPs, excellent bioactivity after a 1-day immersion in c-SBF, hemocompatibility and a high loading capacity (around 80%). They presented ROS scavenging properties, and both the unloaded and ART-loaded NPs significantly promoted cell proliferation even at high concentrations of NPs (125 µg/mL). The ART-loaded Ce-doped NPs with the highest amount of cerium slightly restricted cell proliferation after 7 days of culture, but the difference was not significant compared with the control untreated cells.

Synthesis and Characterization of Mesoporous Mg- and Sr-Doped Nanoparticles for Moxifloxacin Drug Delivery in Promising Tissue Engineering Applications.

Mesoporous silica-based nanoparticles (MSNs) are considered promising drug carriers because of their ordered pore structure, which permits high drug loading and release capacity. The dissolution of Si and Ca from MSNs can trigger osteogenic differentiation of stem cells towards extracellular matrix calcification, while Mg and Sr constitute key elements of bone biology and metabolism. The aim of this study was the synthesis and characterization of sol-gel-derived MSNs co-doped with Ca, Mg and Sr. Their physico-chemical properties were investigated by X-ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDX), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence spectroscopy (XRF), Brunauer Emmett Teller and Brunauer Joyner Halenda (BET/BJH), dynamic light scattering (DLS) and ζ-potential measurements. Moxifloxacin loading and release profiles were assessed with high performance liquid chromatography (HPLC) cell viability on human periodontal ligament fibroblasts and their hemolytic activity in contact with human red blood cells (RBCs) at various concentrations were also investigated. Doped MSNs generally retained their textural characteristics, while different compositions affected particle size, hemolytic activity and moxifloxacin loading/release profiles. All co-doped MSNs revealed the formation of hydroxycarbonate apatite on their surface after immersion in simulated body fluid (SBF) and promoted mitochondrial activity and cell proliferation.

Effect of Sintering Temperature of Bioactive Glass Nanoceramics on the Hemolytic Activity and Oxidative Stress Biomarkers in Erythrocytes.

INTRODUCTION: The nature of the surface is critical in determining the biological activity of silica powders. A novel correlation between toxicity and surface properties of bioactive glass ceramics (BGCs) synthesized via the sol-gel method was attempted in this study. METHODS: The behavior of BGCs after their attachment to the surface of red blood cells (RBCs) was evaluated and their toxic effects were determined based on hemolysis, membrane injury via anti-phosphotyrosine immunoblot of Band 3, lipid peroxidation, potential to generate reactive oxygen species, and antioxidant enzyme production. In particular, three BGCs were synthesized and treated at three sintering temperatures (T1 = 835 °C, T2 = 1000 °C and T3 = 1100 °C) to investigate possible relation between surface charge or structure and hemolytic potential. RESULTS: Their toxicity based on hemolysis was dose dependent, while BGC-T2 had the best hemocompatibility in compare with the other BGCs.No BGCs in dosages lower than 0.125 mg/mL could damage erythrocytes. On the other hand, all BGCs promoted the production of reactive oxygen species in certain concentrations, with the BGC-T2 producing the lowest ROS and increasing the glutathione levels in RBCs protecting their damage. CONCLUSIONS: The results suggest that various factors such as size, a probable different proportion of surface silanols, a balanced mechanism between calcium and magnesium cellular uptake or the different crystalline nature may have contributed to this finding; however, future research is needed to clarify the underlying mechanisms.

Effect of ion doping in silica-based nanoparticles on the hemolytic and oxidative activity in contact with human erythrocytes.

AIM: The aim of this study was the synthesis of ion doped silica-based nanoparticles and the evaluation of their toxic effect on erythrocytes. MATERIALS & METHODS: Their synthesis was performed using the sol-gel method, by the progressive addition of calcium, magnesium and copper ions on pure silica nanoparticles. The toxicity evaluation was based on hemolysis, lipid peroxidation, ROS, H2O2 species and antioxidant enzyme production. RESULTS: The addition of Mg and Cu in the SNs presented better hemocompatibility by protecting erythrocytes from oxidative stress. CONCLUSION: Ion doping with magnesium in the investigated calcium silicate system induces a protective effect in erythrocyte membrane in compare with pure silica nanoparticles.

Effect of ethanol/TEOS ratios and amount of ammonia on the properties of copper-doped calcium silicate nanoceramics.

Calcium magnesium silicate glasses could be suggested for the synthesis of scaffolds for hard tissue regeneration, as they present a high residual glassy phase, high hardness values and hydroxyapatite-forming ability. The use of trace elements in the human body, such as Cu, could improve the biological performance of such glasses, as Cu is known to play a significant role in angiogenesis. Nano-bioceramics are preferable compared to their micro-scale counterparts, because of their increased surface area, which improves both mechanical properties and apatite-forming ability due to the increased nucleation sites provided, their high diffusion rates, reduced sintering time or temperature, and high mechanical properties. The aim of the present work was the evaluation of the effect of different ratios of Ethanol/TEOS and total amount of the inserted ammonia to the particle size, morphology and bioactive, hemolytic and antibacterial behavior of nanoparticles in the quaternary system SiO2-CaO-MgO-CuO. Different ratios of Ethanol/TEOS and ammonia amount affected the size and morphology of bioactive nanopowders. The optimum materials were synthesized with the highest ethanol/TEOS ratio and ammonia amount as verified by the enhanced apatite-forming ability and antibacterial and non-hemolytic properties.