Synthesis, Processing and the Effect of Thermal Treatment on the Solubility, Antioxidant Potential and Cytocompatibility of Y2O3 and CeO2 doped SiO2-SrO-Na2O Glass-Ceramics.

Thermal treatment of a 0.52SiO2-0.24SrO-0.24-xNa2O-xMO glass-ceramic series (where x = 0.08 and MO = Y2O3 or CeO2) was conducted in order to synthesize yttrium (Y3+) and cerium (Ce3+) crystalline species that may act as radical oxygen specie (ROS) scavengers. The prominent phase for the Control is a sodium-strontium-silicate while the experimental glass-ceramics (HY, YCe, and HCe) present sodium-Y/Ce-silicate and oxide phases. Disk shrinkage during thermal processing ranges from 1-7% for Control, HY, YCe, and HCe in both diameter and thickness. Solubility studies determined that the release of Si4+ and Na+ are greatest from the Control disks which peaks at 1550 µg/mL. Release from the Y3+ and Ce3+ glass-ceramics reached 320 µg/mL for Si4+ and 630 µg/mL for Na+. The range of antioxidant capacity (ABTS assay) for all samples was 0.31-3.9 mMTE. No significant reduction in MC 3T3 Osteoblast cell viability was observed for any composition tested.

In vitro evaluation of novel titania-containing borate bioactive glass scaffolds.

Titanium-containing borate bioactive glass scaffolds (0, 5, 15, and 20 mol %, identified as BRT0, BRT1, BRT3, and BRT4) with a microstructure similar to that of human trabecular bone were prepared and evaluated in vitro for potential bone loss applications in revision total knee arthroplasty (rTKA). Methyl thiazolyl tetrazolium (MTT) cell viability assays of scaffold ion release extracts revealed that BRT0 scaffolds (0 mol % titanium) inhibited cell proliferation and activity at day 14. At day 30, all scaffold extracts decreased cell proliferation and activity significantly. However, live/dead cell assay results demonstrated that degradation products from all the scaffolds had no inhibitory effect on cell viability. Significant bactericidal efficacies of BRT3 extracts against Escherishia coli (Gram-negative) and BRT1 extracts against Staphylococcus aureus and Staphylococcus epidermidis (both Gram-positive bacteria) were demonstrated. Finally, evaluation of the cell/bioactive glass surface interactions showed well-spread cells on the surface of the BRT3 glass discs and BRT1 and BRT3 scaffolds, when compared to BRT0 and BRT4 scaffolds. The results indicate that by changing the Ti4+ :B3+ ratio, the ion release and consequently cell proliferation could be improved. in vitro results in this study demonstrate that BRT3 scaffolds could be a promising candidate for addressing bone loss in rTKAs; however, in vivo studies would be required to evaluate the effect of a dynamic environment on the cell and tissue response to the fabricated scaffolds.

Investigating the effect of TiO2 on the structure and biocompatibility of bioactive glass.

Titanium (Ti4+ ) containing materials have been widely used in medical applications due to its associated bioactivity in vivo. This study investigates the replacement of Si4+ with Ti4+ within the system SiO2 -Na2 O-CaO-P2 O5 to determine its influence on glass structure. This strategy was conducted in order to control the glass solubility to further improve the cellular response. Ti4+ incorporation was found to have little influence on the glass transition temperature (Tg = 520 ± 8°C) and magic angle spinning-nuclear magnetic resonance (MAS-NMR) shifts (-80 ppm) up to additions of 18 wt %. However, at 30 wt % the Tg increased to 600°C and MAS-NMR spectra shifted to -88 ppm. There was also an associated reduction in glass solubility as a function of Ti4+ incorporation as determined by inductively coupled plasma optical emission spectroscopy where Si4+ (1649-44 mg/L) and Na+ (892-36 mg/L) levels greatly reduced while Ca2+ (3-5 mg/L) and PO43- (2-7 mg/L) levels remained relatively unchanged. MC3T3 osteoblasts were used for cell culture testing and it was determined that the Ti4+ glasses increased cell viability and also facilitated greater osteoblast adhesion and proliferation to the glass surface compared to the control glass. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1703-1712, 2016.

Antibacterial properties of poly (octanediol citrate)/gallium-containing bioglass composite scaffolds.

Bioactive glasses may function as antimicrobial delivery systems through the incorporation and subsequent release of therapeutic ions. The aim of this study was to evaluate the antimicrobial properties of a series of composite scaffolds composed of poly(octanediol citrate) with increased loads of a bioactive glass that releases zinc (Zn(2+)) and gallium (Ga(3+)) ions in a controlled manner. The antibacterial activity of these scaffolds was investigated against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The ability of the scaffolds to release ions and the subsequent ingress of these ions into hard tissue was evaluated using a bovine bone model. Scaffolds containing bioactive glass exhibited antibacterial activity and this increased in vitro with higher bioactive glass loads; viable cells decreased to about 20 % for the composite scaffold containing 30 % bioactive glass. The Ga(3+) release rate increased as a function of time and Zn(2+) was shown to incorporate into the surrounding bone.

Investigating the effect of silver coating on the solubility, antibacterial properties, and cytocompatibility of glass microspheres.

Silver (Ag) coatings have been incorporated into many medical materials due to its ability to eradicate harmful microbes. In this study, glass microspheres (SiO2-Na2O-CaO-Al2O3) were synthesized and employed as substrates to investigate the effect Ag coating has on glass solubility and the subsequent biological effects. Initially, glasses were amorphous with a glass transition point (T(g)) of 605℃ and microspheres were spherical with a mean particle diameter of 120 µm (±27). The Ag coating was determined to be crystalline in nature and its presence was confirmed using scanning electron microscopy and X-ray photoelectron spectroscopy. Ion release determined that Ag-coated (Ag-S) microspheres increased the Na(+) release rate but slightly reduced the Ca(2+) and Si(4+) release compared to an uncoated control (UC-S). Additionally, the Ag-S reduced the pH to just above neutral (7.3-8.5) compared to the UC-S (7.7-9.1). Antibacterial testing determined significant reductions in planktonic Escherichia coli (p = 0.000), Staphylococcus epidermidis (p = 0.000) and Staphylococcus aureus (p = 0.000) growth as a function of the presence of Ag and with respect to maturation (1, 7, and 30 days). Testing for toxicity levels using L929 Fibroblasts determined higher cell viability for the Ag-S at lower concentrations (5 µg/ml); in addition, no significant reduction in cell viability was observed with higher concentrations (15, 30 µg/ml).

Investigating the addition of SiO2-CaO-ZnO-Na2O-TiO2 bioactive glass to hydroxyapatite: Characterization, mechanical properties and bioactivity.

Hydroxyapatite (Ca10(PO4)6(OH)2) is widely investigated as an implantable material for hard tissue restoration due to its osteoconductive properties. However, hydroxyapatite in bulk form is limited as its mechanical properties are insufficient for load-bearing orthopedic applications. Attempts have been made to improve the mechanical properties of hydroxyapatite, by incorporating ceramic fillers, but the resultant composite materials require high sintering temperatures to facilitate densification, leading to the decomposition of hydroxyapatite into tricalcium phosphate, tetra-calcium phosphate and CaO phases. One method of improving the properties of hydroxyapatite is to incorporate bioactive glass particles as a second phase. These typically have lower softening points which could possibly facilitate sintering at lower temperatures. In this work, a bioactive glass (SiO2-CaO-ZnO-Na2O-TiO2) is incorporated (10, 20 and 30 wt%) into hydroxyapatite as a reinforcing phase. X-ray diffraction confirmed that no additional phases (other than hydroxyapatite) were formed at a sintering temperature of 560 ℃ with up to 30 wt% glass addition. The addition of the glass phase increased the % crystallinity and the relative density of the composites. The biaxial flexural strength increased to 36 MPa with glass addition, and there was no significant change in hardness as a function of maturation. The pH of the incubation media increased to pH 10 or 11 through glass addition, and ion release profiles determined that Si, Na and P were released from the composites. Calcium phosphate precipitation was encouraged in simulated body fluid with the incorporation of the bioactive glass phase, and cell culture testing in MC-3T3 osteoblasts determined that the composite materials did not significantly reduce cell viability.

Silver Nanoparticle Coated Bioactive Glasses--Composites with Dex/CMC Hydrogels: Characterization, Solubility, and In Vitro Biological Studies.

Silver (Ag) coated bioactive glass particles (Ag-BG) were formulated and compared to uncoated controls (BG) in relation to glass characterization, solubility and microbiology. X-ray diffraction (XRD) confirmed a crystalline AgNP surface coating while ion release studies determined low Ag release (<2 mg/L). Cell culture studies presented increased cell viability (127 and 102%) with lower liquid extract (50 and 100 ml/ml) concentrations. Antibacterial testing of Ag-BG in E. coli, S. epidermidis and S. aureus significantly reduced bacterial cell viability by 60-90%. Composites of Ag-BG/CMC-Dex Hydrogels were formulated and characterized. Agar diffusion testing was conducted where Ag-BG/hydrogel composites produced the largest inhibition zones of 7 mm (E. coli), 5 mm (S. aureus) and 4 mm (S. epidermidis).

A glass polyalkenoate cement carrier for bone morphogenetic proteins.

This work considers a glass polyalkenoate cement (GPC)-based carrier for the effective delivery of bone morphogenetic proteins (BMPs) at an implantation site. A 0.12 CaO-0.04 SrO-0.36 ZnO-0.48 SiO2 based glass and poly(acrylic acid) (PAA, Mw 213,000) were employed for the fabrication of the GPC. The media used for the water source in the GPC reaction was altered to produce a series of GPCs. The GPC liquid media was either 100 % distilled water with additions of albumin at 0, 2, 5 and 8 wt% of the glass content, 100 % formulation buffer (IFB), and 100 % BMP (150 µg rhBMP-2/ml IFB). Rheological properties, compressive strength, ion release profiles and BMP release were evaluated. Working times (Tw) of the formulated GPCs significantly increased with the addition of 2 % albumin and remained constant with further increases in albumin content or IFB solutions. Setting time (Ts) experienced an increase with 2 and 5 % albumin content, but a decrease with 8 % albumin. Changing the liquid source to IFB containing 5 % albumin had no significant effect on Ts compared to the 8 % albumin-containing BT101. Replacing the albumin with IFB/BMP-2 did not significantly affect Tw. However, Ts increased for the BT101_BMP-2 containing GPCs, compared to all other samples. The compressive strength evaluated 1 day post cement mixing was not affected significantly by the incorporation of BMPs, but the ion release did increase from the cements, particularly for Zn and Sr. The GPCs released BMP after the first day, which decreased in content during the following 6 days. This study has proven that BMPs can be immobilized into GPCs and may result in novel materials for clinical applications.

Investigating the solubility and cytocompatibility of CaO-Na2 O-SiO2 /TiO2 bioactive glasses.

This study aims to investigate the solubility of a series of titanium (TiO2 )-containing bioactive glasses and their subsequent effect on cell viability. Five glasses were synthesized in the composition range SiO2 -Na2 O-CaO with 5 mol % of increments TiO2 substituted for SiO2 . Glass solubility was investigated with respect to (1) exposed surface area, (2) particle size, (3) incubation time, and (4) compositional effects. Ion release profiles showed that sodium (Na(+) ) presented high release rates after 1 day and were unchanged between 7 and 14 days. Calcium (Ca(2+) ) release presented a significant change at each time period and was also composition dependent, where a reduction in Ca(2+) release is observed with an increase in TiO2 concentration. Silica (Si(4+) ) release did not present any clear trends while no titanium (Ti(4+) ) was released. Cell numbers were found to increase up to 44%, compared to the growing control population, with a reduction in particle size and with the inclusion of TiO2 in the glass composition.

Investigating the surface reactivity of SiO2-TiO2-CaO-Na2O/SrO bioceramics as a function of structure and incubation time in simulated body fluid.

This study focuses on evaluating the biocompatibility of a SiO2-TiO2-CaO-Na2O/SrO glass and glass-ceramic series. Glass and ceramic samples were synthesized and characterized using X-ray diffraction. Each material was subject to maturation in simulated body fluid over 1, 7 and 30 days to describe any changes in surface morphology. Calcium phosphate (CaP) deposition was observed predominantly on the Na(+) containing amorphous and crystalline materials, with plate-like morphology. The precipitated surface layer was also observed to crystallize with respect to maturation, which was most evident in the amorphous Na(+) containing glasses, Ly-N and Ly-C. The addition of Sr(2+) greatly reduced the solubility of all samples, with limited CaP precipitation on the amorphous samples and no deposition on the crystalline materials. The morphology of the samples was also different, presenting irregular plate-like structures (Ly-N), needle-like deposits (Ly-C) and globular-like structures (Ly-S). Cell culture analysis presented a significant increase in cell viability with the Na(+) materials, 134%, while the Sr(2+) containing glasses, 60-80% and ceramics, 60-85% presented a general reduction in cell viability, however these reductions were not significant.

Investigating the effect of SiO2-TiO 2-CaO-Na 2O-ZnO bioactive glass doped hydroxyapatite: characterisation and structural evaluation.

The effects of increasing bioactive glass additions, SiO2-TiO2-CaO-Na2O-ZnO up to 25 wt% in increments of 5 wt%, on the physical and mechanical properties of hydroxyapatite (HA) sintered at 900, 1000, 1100 and 1200 °C for 2 h was investigated. Increasing both the glass content and the temperature resulted in increased HA decomposition. This resulted in the formation of a number of bioactive phases. However the presence of the liquidus glass phase did not result in increased densification levels. At 1000 and 1100 °C the additions of 5 wt% glass resulted in a decrease in density which never recovered with increasing glass content. At 1200 °C a cyclic pattern resulted from increasing glass content. There was no direct relationship between strength and density with all samples experiencing no change or a decrease in strength with increasing glass content. Weibull statistics displayed no pattern with increasing glass content.

Characteristics of glass ionomer cements composed of glass powders in CaO-SrO-ZnO-SiO2 system prepared by two different synthetic routes.

Glass ionomer cements (GICs) are composed of an acid degradable glass, polyacrylic acid and water. Sol-gel processing to prepare the glass phase has certain advantages, such as the ability to employ lower synthesis temperatures than melt quenching and glasses that are reported to have higher purity. A previous study reported the effects of glass synthesis route on GIC fabrication. However, in that study, the sol-gel derived glass exhibited a reduced concentration of cations. This study investigates increasing the cation content of a sol-gel derived glass, 12CaO.4SrO.36ZnO.48SiO2 (molar ratio) by heating before aging to reduce dissolution of cations. This glass was prepared by both sol-gel and melt-quenched routes. GICs were subsequently prepared using both glasses. The resultant cement based on the sol-gel derived glass had a shorter working time than the cement based on the melt-quenched one. Contrary to this, setting time was considerably longer for the cement based on the sol-gel derived glass than for the cement based on the melt-quenched one. The cements based on the sol-gel derived glass were stronger in both compression and biaxial flexure than the cements prepared from the melt-quenched glass. The differences in setting and mechanical properties were associated with both cation content in the glass phase and the different surface area of the resultant cements.

Comparison of the Weibull characteristics of hydroxyapatite and strontium doped hydroxyapatite.

The effects of two strontium (Sr) additions, 5% and 10% of the total calcium (Ca) content, on the phase assemblage and Weibull statistics of hydroxyapatite (HA) are investigated and compared to those of undoped HA. Sintering was carried out in the range of 900-1200 °C in steps of 1000 °C in a conventional furnace. Sr content had little effect on the mean particulate size. Decomposition of the HA phase occurred with Sr incorporation, while ß-TCP stabilization was shown to occur with 10% Sr additions. Porosity in both sets of doped samples was at a comparable level to porosity in the undoped HA samples, however the 5% Sr-HA samples displayed the greatest reduction in porosity with increasing temperature while the porosity of the 10% Sr-HA samples remain relatively constant over the full sintering temperature range. The undoped HA samples displayed the greatest Weibull strengths and the porosity was determined to be the major controlling factor. However, with the introduction of decompositional phases in the Sr-HA samples, the dependence of strength on porosity is reduced and the phase assemblage becomes the more dominant factor for Weibull strength. The Weibull modulus is relatively independent of the porosity in the undoped HA samples. The 5% Sr-HA samples experience a slight increase in Weibull modulus with porosity, indicating a possible relationship between the parameters. However the 10% Sr-HA samples show the highest Weibull modulus with a value of approximately 15 across all sintering temperatures. It is postulated that this is due to the increased amount of surface and lattice diffusion that these samples undergo, which effectively smooths out flaws in the microstructure, due to a saturation of Sr content occurring in grain boundary movement.

Evaluation of two novel aluminum-free, zinc-based glass polyalkenoate cements as alternatives to PMMA bone cement for use in vertebroplasty and balloon kyphoplasty.

Vertebroplasty (VP) and balloon kyphoplasty (BKP) are now widely used for treating patients in whom the pain due to vertebral compression fractures is severe and has proved to be refractory to conservative treatment. These procedures involve percutaneous delivery of a bolus of an injectable bone cement either directly to the fractured vertebral body, VB (VP) or to a void created in it by an inflatable bone tamp (BKP). Thus, the cement is a vital component of both procedures. In the vast majority of VPs and BKPs, a poly(methyl methacrylate) (PMMA) bone cement is used. This material has many shortcomings, notably lack of bioactivity and very limited resorbability. Thus, there is room for alternative cements. We report here on two variants of a novel, bioactive, Al-free, Zn-based glass polyalkenoate cement (Zn-GPC), and how their properties compare to those of an injectable PMMA bone cement (SIMPL) that is widely used in VP and BKP. The properties determined were injectability, radiopacity, uniaxial compressive strength, and biaxial flexural modulus. In addition, we compared the compression fatigue lives of a validated synthetic osteoporotic VB model (a polyurethane foam cube with an 8 mm-diameter through-thickness cylindrical hole), at 0-2300 N and 3 Hz, when the hole was filled with each of the three cements. A critical review of the results suggests that the performance of each of the Zn-GPCs is comparable to that of SIMPL; thus, the former cements merit further study with a view to being alternatives to an injectable PMMA cement for use in VP and BKP.

The role of Sr2+ on the structure and reactivity of SrO-CaO-ZnO-SiO2 ionomer glasses.

The suitability of Glass Polyalkenoate Cements (GPCs) for use in orthopaedics is retarded by the presence in the glass phase of aluminium, a neurotoxin. Unfortunately, the aluminium ion plays an integral role in the setting process of GPCs and its absence is likely to hinder cement formation. However, the authors have previously shown that aluminium free GPCs may be formulated based on calcium zinc silicate glasses and these novel materials exhibit significant potential as hard tissue biomaterials. To further improve their potential, and given that Strontium (Sr) based drugs have had success in the treatment of osteoporosis, the authors have substituted Calcium (Ca) with Sr in the glass phase of a series of aluminium free GPCs. However to date little data exists on the effect SrO has on the structure and reactivity of SrO-CaO-ZnO-SiO(2) glasses. The objective of this work was to characterise the effect of the Ca/Sr substitution on the structure of such glasses, and evaluate the subsequent reactivity of these glasses with an aqueous solution of Polyacrylic acid (PAA). To this end (29)Si MAS-NMR, differential scanning calorimetry (DSC), X-ray diffraction, and network connectivity calculations, were used to characterize the structure of four strontium calcium zinc silicate glasses. Following glass characterization, GPCs were produced from each glass using a 40 wt% solution of PAA (powder:liquid = 2:1.5). The working times and setting times of the GPCs were recorded as per International standard ISO9917. The results acquired as part of this research indicate that the substitution of Ca for Sr in the glasses examined did not appear to significantly affect the structure of the glasses investigated. However it was noted that increasing the amount of Ca substituted for Sr did result in a concomitant increase in setting times, a feature that may be attributable to the higher basicity of SrO over CaO.