Regulation of the antibiotic elution profile from tricalcium phosphate bone cement by addition of bioactive glass.

This work aimed at tailoring of different properties of antibacterial drug delivery Ca-phosphate cements by incorporation of bioactive glass (BG). The cements were prepared from beta-tricalcium phosphate cement (ß-TCP) and BG based on 50 SiO2-20 CaO-15 Na2O-7 B2O3-4 P2O5-4 Al2O3 wt% with different percentages of BG [5, 10, 15, and 20% (w/w)]. The composite cements were characterized by XRD, FTIR, and TEM. Moreover, in vitro bioactivity and biodegradation were evaluated in the simulated body fluid (SBF) at 37 °C. In addition, physical properties and mechanical strength were determined. Also, the effect of glass addition on the drug release profile was examined using gentamicin. Finally, the antimicrobial activity was studied against Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumonia bacteria, one unicellular fungal strain (Candida albicans), and one multicellular fungal strain (Mucor racemosus). The results showed that after soaking in SBF, the compression strength values ranged from 14 to 36 MPa, the bulk densities and porosities were within 1.35 to 1.49 g/cm3 and 51.3 to 44.71%, respectively. Furthermore, gentamicin was released in a sustained manner, and BG decreased the released drug amount from ~ 80% (in pure ß-TCP) to 47-53% in the composite cements. A drug release profile that is sustained by all samples was achieved. The antimicrobial test showed good activity of gentamicin-conjugated cements against bacteria and fungi used in this study. Additionally, cytotoxicity results proved that all samples were safe on MG-63 cells up to 50 µg/mL with no more than 7-12% dead cells. From the view of the physico-mechanical properties, bioactivity, biodegradation, and drug release rate, 20BG/ß-TCP sample was nominated for practical bone grafting material, where it showed appropriate setting time and a relatively high mechanical strength suitable for cancellous bone.

Synthesise and Characterization of Cordierite and Wollastonite Glass-Ceramics Derived from Industrial Wastes and Natural Raw Materials.

Industrial waste is one of the primary sources that harm the environment, and this topic has occupied many scientists on how to take advantage of these wastes or dispose of them and create a clean environment. By-pass cement dust is considered one of the most dangerous industrial wastes due to its fine granular size and its volatilization in the air, which causes severe environmental damage to human and animal health, and this is the reason for choosing the current research point. In this article, eight samples of glass-ceramics were prepared using by-pass cement dust and natural raw materials known as silica sand, magnesite, and kaolin. Then melted by using an electric furnace which was adjusted at a range of temperatures from 1550 to 1600 °C for 2 to 3 h; the samples were cast and were subjected to heat treatment at 1000 °C for 2 h based on the DTA results in order to produce crystalline materials. Various techniques were used to study the synthesized glass-ceramic samples, including differential thermal analysis (DTA), X-ray diffraction (XRD), scanning electron microscope (SEM), and thermal expansion coefficient (CTE). X-ray analysis showed that the phases formed through investigated glass-ceramic samples consisted mainly of ß- wollastonite, parawollastonite, diopside, anorthite, and cordierite. It was noticed that ß- the wollastonite phase was formed first and then turned into parawollastonite, and also, the anorthite mineral was formed at low temperatures before the formation of the diopside mineral. SEM showed that the formed microstructure turned from a coarse grain texture to a fine-grained texture, by increasing the percentage of cordierite. It also showed that the increase in time at the endothermic temperature significantly affected the crystalline texture by giving a fine-grained crystalline texture. The linear thermal expansion measurements technique used for the studied glass-ceramic samples gives thermal expansion coefficients ranging from 6.2161 × 10-6 to 2.6181 × 10-6 C-1 (in the range of 20-700 °C), and it decreased by increasing cordierite percent.

Effect of Ce-doped bioactive glass/collagen/chitosan nanocomposite scaffolds on the cell morphology and proliferation of rabbit's bone marrow mesenchymal stem cells-derived osteogenic cells.

BACKGROUND: Cerium-containing materials have wide applications in the biomedical field, because of the mimetic catalytic activities of cerium. The study aims to deeply estimate the biocompatibility of different scaffolds based on Ce-doped nanobioactive glass, collagen, and chitosan using the first passage of rabbit bone marrow mesenchymal stem cells (BM-MSCs) directed to osteogenic lineage by direct and indirect approach. One percentage of glass filler was used (30 wt. %) in the scaffold, while the percentage of CeO2 in the glass was ranged from 0 to 10 mol. %. Cytotoxicity was evaluated by monitoring of cell morphological changes and reduction in cell proliferation activity of BMMSCs maintained under osteogenic condition using proliferation assays, MTT assay for the direct contact of cells/scaffolds twice in a week, trypan blue and hemocytometer cell counting for indirect contact of cells/scaffolds extracts at day 7. Cell behaviors growth, morphology characteristics were monitored daily under a microscope and cell counting were conducted after 1 week of the incubation of the cells with the extracts of the four composite scaffolds in the osteogenic medium at the end of the week. RESULTS: Showed that at 24 h after direct contact with composite scaffold, all scaffolds showed proliferation of cells > 50% and increased in cell density on day 7. The scaffold of the highest percentage of CeO2 in bioactive glass nanoparticles (sample CL/CH/C10) showed the lowest inhibition of cell proliferation (< 25%) at day 7. Moreover, the indirect cell viability test showed that all extracts from the four composite scaffolds did not demonstrate a toxic effect on the cells (inhibition value < 25%). CONCLUSION: The addition of CeO2 to the glass composition improved the biocompatibility of the composite scaffold for the proliferation of rabbit bone marrow mesenchymal stem cells directed to osteogenic lineage.

Use of Arc Furnace Slag and Ceramic Sludge for the Production of Lightweight and Highly Porous Ceramic Materials.

The utility of recycling some intensive industries' waste materials for producing cellular porous ceramic is the leading aim of this study. To achieve this purpose, ceramic samples were prepared utilizing both arc furnace slag (AFS) and ceramic sludge, without any addition of pure chemicals, at 1100 °C. A series of nine samples was prepared via increasing AFS percentage over sludge percentage by 10 wt.% intervals, reaching 10 wt.% sludge and 90 wt.% AFS contents in the ninth and last batch. The oxide constituents of waste materials were analyzed using XRF. All synthesized samples were investigated using XRD to detect the precipitated minerals. The developed phases were ß-wollastonite, quartz, gehlenite, parawollastonite and fayalite. The formed crystalline phases were changed depending on the CaO/SiO2 ratio in the batch composition. Sample morphology was investigated via scanning electron microscope to identify the porosity of the prepared ceramics. Porosity, density and electrical properties were measured; it was found that all these properties were dependent on the composition of starting materials and formed phases. When increasing CaO and Al2O3 contents, porosity values increased, while increases in MgO and Fe2O3 caused a decrease in porosity and increases in dielectric constant and electric conductivity. Sintering of selected samples at different temperatures caused formation of two polymorphic structures of wollastonite, either ß-wollastonite (unstable) or parawollastonite (stable). ß-wollastonite transformed into parawollastonite at elevated temperatures. When increasing the sintering temperature to 1150 °C, a small amount of fayalite phase (Fe2SiO4) was formed. It was noticed that the dielectric measurements of the selected sintered samples at 1100 °C were lower than those recorded when sintering temperatures were 1050 °C or 1150 °C.

Role of alkali metal oxide type on the degradation and in vivo biocompatibility of soda-lime-borate bioactive glass.

In this work, it is the first time to study the effect of replacing of Na2 O by a fixed amount of Li2 O or K2 O in soda-lime-borate glass on its in vivo biocompatibility. The glass composition was based on xM2 O-20x Na2 O20 CaO60 B2 O3 , (wt %), where, M2 OLi2 O and K2 O, and consequently, samples encoded BN100, BK50, and BL50. The degradation test was carried out in 0.25 M K2 HPO4 solution. The in vivo test was performed in the femoral bone defect of Sprague-Dawley adult male rat. Following up bone formation was conducted by the histological analyses and bone formation markers (alkaline phosphatase [ALP] and osteocalcin [OCN]). Furthermore, the glass effect on the liver and kidney functions was addressed in this study using (alanine transaminase [ALT] and aspartate transaminase [AST]) and (urea and creatinine), respectively. The results of the degradation test showed that the glass dissolution rate was increased by incorporating of K2 O, and its ion release was occurred by a diffusion-controlled process. Moreover, in vivo bioactivity test showed that serum activity of ALP, OCN level, and the newly formed bone was higher in BL50-implanted group than that of BN100 andBK50at 3 w and 6 w post-surgery. As well as, implantation of all glass samples in the femoral bone defect did not alter the liver and kidney functions. In conclusion, the synthesized borate glass was well served as a controlled delivery system for Li+ ion release, which enhanced bone formation as shown from the bone formation markers (ALP and OCN).

The combined antibacterial and anticancer properties of nano Ce-containing Mg-phosphate ceramic.

AIM: This paper was mainly aimed at synthesis of Ce-containing nano-Mg-phosphate ceramic as a multifunctional material. MATERIALS AND METHODS: Two ceramics based on Mg3(PO4)2 and Ce0.2Mg2.8(PO4)2 formulas (MP and MP-C, respectively) were synthesized. The synthesized powders were characterized by XRD, TEM, Zeta potential, and FTIR. Also, their dissolution behavior was tested in Tris-HCl buffer solution. Moreover, the antimicrobial efficacy was evaluated against gram-positive bacteria (Bacillus sphaericus MTCC 511 &Staphylococcus aureus MTCC 87) and gram-negative bacteria (Enterobacter aerogenes MTCC 111 &Pseudomonas aeruginosa MTCC 1034) using dick diffusion assay and microdilution method. Furthermore, the cell viability test was performed for the ceramics on Vero cells (African green monkey kidney cells), and their antitumor activity was determined by PC3 cell line (prostatic cancer). Also, the cellular uptake was determined by the flow cytometry. KEY FINDINGS: The results showed that the substitution of Mg by Ce decreased the particle size from 40 to 90 nm for MP sample to 2-10 nm for MP-C sample and increased the degradation rate. Both samples showed excellent antimicrobial activities. Moreover, MP demonstrated more cell viability than MP-C on Vero cells at high concentrations, whereas, MP-C showed more antitumor activity on PC3 cells than MP sample. Moreover, MP-C showed a higher cell uptake than MP due to its smaller size and more negative charge. SIGNIFICANCE: Mg-phosphate ceramic can be used in this study successfully as a delivery system for cerium ions and showed a high antitumor activity, which makes it highly recommended as safe and effective cancer treatment materials.

Green synthesis of bacterial cellulose/bioactive glass nanocomposites: Effect of glass nanoparticles on cellulose yield, biocompatibility and antimicrobial activity.

Despite the advantages of bacterial cellulose (BC) over traditional cellulose, its low yield and little bioactivity makes a limitation to be used in an industrial scale. This paper was mainly dual aimed to increase the BC yield using a nanobioactive glass (NBG), and in situ synthesize BC/NBG bioactive nanocomposites by a novel and simple green method. Accordingly, the composites were prepared via in situ fermentation approach by incorporation of NBG particles into BC producing culture medium. The effect of NBG addition on the production process of cellulose, biocompatibility, bioactivity and antimicrobial activity were investigated. The results showed that NBG was enhanced and increased the BC yield and this has been achieved by maintaining these NBG on the pH value of the culture medium during the fermentation period. Moreover, it was effectively improved biocompatibility and antimicrobial properties of BC. This study evidenced that BC/NBG composite can be expected to be widely applied in biomedical industries such as bone regeneration and wound healing with the unique of being not harmful to humans.

Toward Rational Design of Novel Anti-Cancer Drugs Based on Targeting, Solubility, and Bioavailability Exemplified by 1,3,4-Thiadiazole Derivatives Synthesized Under Solvent-Free Conditions.

The 1,3,4-thiadiazole derivatives (9a-i) were synthesized under solvent free conditions and their chemical composition was confirmed using different spectral tools (IR, Mass, and NMR spectrometry). All the synthesized compounds were screened for their anti-cancer potentiality over human breast carcinoma (MCF-7) and human lung carcinoma (A-549). Most of the tested compounds showed remarkable anti-breast cancer activity. However, compound 4 showed the most anti-lung cancer activity. Then, compounds with cytotoxic activity ≥ 80% over breast and lung cells were subjected to investigate their specificity on human normal skin cell line (BJ-1). Compounds 9b and 9g were chosen owing to their high breast anti-cancer efficacy and their safety, in order to study the possible anti-cancer mode of action. Otherwise, drug delivery provides a means to overcome the low solubility, un-targeted release, and limited bioavailability of the prepared 1,3,4-thiadiazole drug-like substances. Compounds 9b and 9g were chosen to be encapsulated in Na-alginate microspheres. The release profile and mechanism of both compounds were investigated, and the results revealed that the release profiles of both microspheres showed a sustained release, and the release mechanism was controlled by Fickian diffusion. Accordingly, these compounds are promising for their use in chemotherapy for cancer treatment, and their hydrophilicity was improved by polymer encapsulation to become more effective in their pharmaceutical application.

In vitro drug release behavior of Ce-doped nano-bioactive glass carriers under oxidative stress.

Ce-containing bioactive glasses are known to decrease reactive oxygen activities inside the body. That is because of their excellent catalytic activities which come from the fast interchange of Ce3+/Ce4+ oxidation states. This research was mainly aimed at preparing new Ce-doped nano-bioactive glasses based on 60SiO2-(10-x)B2O3-25CaO-5P2O5-xCeO2, in mole% (x = 0 and 5 mol%) as multifunctional bone fillings. Moreover, the glasses were used as a delivery system for ciprofloxacin to intensely solve the bone infection complications. Nevertheless, there were no previous works studied of the nature immersing solution effect on the drug release behavior from Ce-doped nano-bioactive glass carriers. Therefore, phosphate-free and phosphate-containing buffer solutions with/without superoxide species (H2O2) were used to investigate the efficacy of this drug delivery system in different environment. The results showed that Ce addition enhanced the formation of apatite layer and cell viability. Moreover, the percentage of released drug was apparently affected by the glass composition and nature of soaking fluid, specifically, in the media containing superoxide species (H2O2). In conclusion, the prepared Ce-doped glass nanoparticles illustrated multifunctional bone filling material, but when it intended to be utilized as a drug delivery system, the nature of surrounding medium have to be taken into consideration.

Bioactive glass nanoparticles designed for multiple deliveries of lithium ions and drugs: Curative and restorative bone treatment.

Lithium modified bioactive glass nanoparticles were prepared for multiple deliveries of lithium ions and drugs. The particle size, structure and thermal behavior of nanoparticles were analyzed using TEM, FTIR and DSC respectively. The porosity% and specific surface area of glass nanoparticles were about 68.6% and 224.92 (m(2)/g), respectively. The in vitro bioactivity evaluation in SBF revealed that glass nanoparticles were capable of inducing apatite layer over their surfaces. This could be considered as a good indicator for their future abilities to regenerate bone tissue in vivo. Also, lithium ions were released from glass nanoparticles via diffusion controlled process which could activate Wnt signaling pathway and enhance osteogenesis. As a final point, the possibility of utilizing the glass nanoparticles as a controlled delivery device for vancomycin or 5-FU was verified. Fitting vancomycin or 5-FU release profiles to various mathematical models pointed out that both drugs were released by a diffusion-controlled mode.