Investigating the effect of germanium on the structure of SiO2-ZnO-CaO-SrO-P2O5 glasses and the subsequent influence on glass polyalkenoate cement formation, solubility and bioactivity.

A series of germanium (Ge)-containing glasses were synthesized based on a starting glass composition of SiO2-ZnO-CaO-SrO-P2O5. Additions of GeO2 (6 and 12 mol%) were incorporated at the expense of SiO2, which retained the amorphous character, and each glass was processed to present similar particle size and surface area. Glass characterization using x-ray photoelectron spectroscopy (XPS) and magic angle spinning nuclear magnetic resonance (MAS-NMR) determined that the addition of GeO2 increased the fraction of lower Q-speciation and subsequently the concentration of non-bridging oxygens (NBO). Glass Polyalkenoate Cements (GPC) were formulated from each glass with 40, 50 and 60 wt% PAA, and presented time dependent solubility profiles (1, 10, 100, 1000 h) for the release of Si4+ (4-140 mg/l), Ca2+ (1-8 mg/l), Zn2+ (<6 mg/l), Sr2+ (2-37 mg/l), PO43- (2-43 mg/l) and Ge4+ (20-911 mg/l) and attained pH values close to 7.5 after 1000 h. Ge-GPCs containing 40 wt% polyacrylic acid (PAA) presented appropriate working time (Tw) and setting times (Ts), and the corresponding compressive strengths ranged from (14-30 MPa). The Ge-GPCs (40, 50 wt%) presented a linear increase (R2-0.99) with respect to time. Simulated Body Fluid (SBF) testing resulted in the Ge-GPCs encouraging the precipitation of crystalline hydroxyapatite on the GPC surface, more evidently after 100 and 1000 h incubation.

Antibacterial and antifungal potential of Ga-bioactive glass and Ga-bioactive glass/polymeric hydrogel composites.

A bioactive glass series (0.42SiO2 -0.10Na2 O-0.08CaO-(0.40 - x)ZnO-(x)Ga2 O3 ) was synthesized, and it is efficacy against the Gram (-ve) bacteria Escherichia coli (E. coli), the Gram (+ve) bacteria Staphylococcus aureus (S. aureus), and the fungus Candida albicans (C. albicans), were characterized through liquid broth analysis. The glass series was also seeded in CMC-Dex hydrogels at three different loadings (0.05, 0.10, and 0.25 m2 ), and the antibacterial and antifungal efficacies of the resulting composites were characterized using both liquid broth and agar diffusion analysis. Liquid broth analysis was conducted using liquid extracts, which for glass samples were obtained after incubation for up to 30 days in both ultrapure water and phosphate buffered saline (PBS), while glass-hydrogel extracts were obtained solely in PBS. Glass extracts (water) decreased C. albicans viability, while those obtained in PBS decreased the viability of both E. coli and C. albicans. Glass-hydrogel extracts exhibited slight inhibition of E. coli and C. albicans. However, none of the liquid extracts decreased S. aureus viability. Glass-hydrogel composites produced inhibition zones in all three microbial cultures, with the greatest efficacy against C. albicans. The results of this study suggest these materials have potential as bone void-filling materials which display antifungal, and possibly, antibacterial properties. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1102-1113, 2017.

Structural characterization and anti-cancerous potential of gallium bioactive glass/hydrogel composites.

A bioactive glass series (0.42SiO2-0.10Na2O-0.08CaO-(0.40-X)ZnO-(X)Ga2O3) was incorporated into carboxymethyl cellulose (CMC)/dextran (Dex) hydrogels in three different amounts (0.05, 0.10, and 0.25m(2)), and the resulting composites were characterized using transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and (13)C Cross Polarization Magic Angle Spinning Nuclear Magnetic Resonance (CP MAS-NMR). Composite extracts were also evaluated in vitro against MG-63 osteosarcoma cells. TEM confirmed glass distribution throughout the composites, although some particle agglomeration was observed. DSC revealed that glass composition and content did have small effects on both Tg and Tm. MAS-NMR revealed that both CMC and Dex were successfully functionalized, that cross-linking occurred, and that glass addition did slightly alter bonding environments. Cell viability analysis suggested that extracts of the glass and composites with the largest Ga-content significantly decreased MG-63 osteosarcoma viability after 30days. This study successfully characterized this composite series, and demonstrated their potential for anti-cancerous applications.

Bioactivity of Y2O3 and CeO2 doped SiO2-SrO-Na2O glass-ceramics.

The bioactivity of yttrium and cerium are investigated when substituted for Sodium (Na) in a 0.52SiO2-0.24SrO-0.24-xNa2O-xMO glass-ceramics (where x = 0.08 and MO = Y2O3 or CeO2). Bioactivity is monitored through pH and inductively coupled plasma-optical emission spectrometry where pH of simulated body fluid ranged from 7.5 to 7.6 and increased between 8.2 and 10.0 after 14-day incubation with the glass-ceramic disks. Calcium (Ca) and phosphorus (P) levels in simulated body fluid after incubation with yttrium and cerium containing disks show a continual decline over the 14-day period. In contrast, Con disks (not containing yttrium or cerium) caused the elimination of Ca in solution after 1 day and throughout the incubation period, and initially showed a decline in P levels followed by an increase at 14 days. Scanning electron microscopy and energy dispersive spectroscopy confirmed the presence of Ca and P on the surface of the simulated body fluid-incubated disks and showed precipitates on Con and HCe (8 mol% cerium) samples. Cell viability of MC3T3 osteoblasts was not significantly affected at a 9% extract concentration. Optical microscopy after 24 h cell incubation with disks showed that Con samples do not support osteoblast or Schwann cell growth, while all yttrium and cerium containing disks have direct contact with osteoblasts spread across the wells. Schwann cells attached in all wells, but only showed spreading with the HY-S (8 mol% yttrium, heated to sintering temperature) and YCe (4 mol% yttrium and cerium) disks. Scanning electron microscopy of the compatible disks shows osteoblast and sNF96.2 Schwann cells attachment and spreading directly on the disk surfaces.

Synthesis, characterization, and in vitro cytocompatibility of Ga-bioactive glass/polymer hydrogel composites.

A bioactive glass series (0.42SiO2-0.10Na2O-0.08CaO-(0.40-x)ZnO-(x)Ga2O3) was incorporated in carboxymethyl cellulose-dextran hydrogels at three different loadings (0.05, 0.10, and 0.25 m2), and the resulting composites were characterized using scanning electron microscopy, physical swelling characteristics, and inductively coupled plasma optical emission spectroscopy. In vitro cytocompatibility was also evaluated for composite extracts in contact with L-929 mouse fibroblasts and MC3T3-E1 human osteoblasts. Scanning electron microscopy confirmed that glass particles were distributed throughout the hydrogels, and swelling studies showed that glass presence can increase the amount of fluid that can be absorbed by the hydrogels after seven days of immersion in phosphate-buffered saline by up to 180%. Several trends were observed in the inductively coupled plasma optical emission spectroscopy data, with the most important being the release of Ga3+ from both Ga-containing glasses at all three loadings, with a maximum of 4.7 mg/L released after 30 days of incubation in phosphate-buffered saline. Cell viability analysis suggested that most composite extracts did not decrease neither fibroblast nor osteoblast viability. These results indicate that it is possible to embed bioactive glass particles into carboxymethyl cellulose-dextran hydrogels, and upon submersion in aqueous media, release ions from the glass particles that may elicit therapeutic effects.

Investigating the structure and biocompatibility of niobium and titanium oxides as coatings for orthopedic metallic implants.

Applying sol gel based coatings to orthopedic metallic implant materials can significantly improve their properties and lifespan in vivo. For this work, niobium (Nb2O5) and titanium (TiO2) oxides were prepared via solution processing in order to determine the effect of atomic arrangement (amorphous/crystalline) on bioactivity. Thermal evaluation on the synthesized materials identified an endotherm for Nb2O5 at 75 °C with 40% weight loss below 400 °C, and minimal weight loss between 400 and 850 °C. Regarding TiO2 an endotherm was present at 92 °C with 25% weight loss below 400 °C, and 4% between 400 and 850 °C. Phase evolution was determined using High Temperature X-ray Diffraction (HT-XRD) where amorphous-Nb2O5 (450 °C), hexagonal-Nb2O5 (525 °C), orthorhombic-Nb2O5 (650 °C), amorphous-TiO2 (275 °C) and tetragonal TiO2 (500 °C) structures were produced. Simulated body fluid (SBF) testing was conducted over 1, 7 and 30 days and resulted in positive chemical and morphological changes for crystalline Nb2O5 (525 °C) and TiO2 (500 °C) after 30 days of incubation. Rod-like CaP deposits were observed on the surfaces using Scanning Electron Microscopy (FE-SEM) and Grazing Incidence-X-ray Diffraction (GI-XRD) shows that the deposits were X-ray amorphous. Cell viability was higher with the TiO2 (122%) samples when compared to the growing cell population while Nb2O5 samples exhibited a range of viability (64-105%), partially dependent on materials atomic structure.

Investigating the influence of Na+ and Sr2+ on the structure and solubility of SiO2-TiO2-CaO-Na2O/SrO bioactive glass.

This study was conducted to determine the influence that network modifiers, sodium (Na+) and strontium (Sr2+), have on the solubility of a SiO2-TiO2-CaO-Na2O/SrO bioactive glass. Glass characterization determined each composition had a similar structure, i.e. bridging to non-bridging oxygen ratio determined by X-ray photoelectron spectroscopy. Magic angle spinning nuclear magnetic resonance (MAS-NMR) confirmed structural similarities as each glass presented spectral shifts between -84 and -85 ppm. Differential thermal analysis and hardness testing revealed higher glass transition temperatures (Tg 591-760 °C) and hardness values (2.4-6.1 GPa) for the Sr2+ containing glasses. Additionally the Sr2+ (~250 mg/L) containing glasses displayed much lower ion release rates than the Na+ (~1,200 mg/L) containing glass analogues. With the reduction in ion release there was an associated reduction in solution pH. Cytotoxicity and cell adhesion studies were conducted using MC3T3 Osteoblasts. Each glass did not significantly reduce cell numbers and osteoblasts were found to adhere to each glass surface.

Comparison of a SiO2-CaO-ZnO-SrO glass polyalkenoate cement to commercial dental materials: ion release, biocompatibility and antibacterial properties.

Ion Release and biocompatibility of a CaO-SrO-ZnO-SiO2 (BT 101) based glass polyalkenoate cement (GPC) was compared against commercial GPCs, Fuji IX and Ketac Molar. The radiopacity (R) was similar for each material, 2.0-2.8. Ion release was evaluated on each material over 1, 7, 30 and 90 days. BT 101 release included Ca (23 mg/L), Sr (23 mg/L) Zn (13 mg/L), Si (203 mg/L). Fuji IX release includes Ca (0.7 mg/L), Al (3 mg/L) Si (26 mg/L), Na (60 mg/L) and P (0.5 mg/L) while Ketac Molar release includes Ca (1 mg/L), Al (0.6 mg/L) Si (23 mg/L), Na (76 mg/L) and P (0.7 mg/L). Simulated body fluid trials revealed CaP surface precipitation on BT 101. No evidence of precipitation was found on Fuji IX or Ketac Molar. Cytotoxicity testing found similar cell viability values for each material (~60 %, P = 1.000). Antibacterial testing determined a reduced CFU count with BT 101 (2.5 × 10³) when compared to the control bacteria (2.4 × 104), Fuji IX (1.5 × 104) and Ketac Molar (1.2 × 104).

Aluminium-free glass polyalkenoate cements: ion release and in vitro antibacterial efficacy.

Glass polyalkenoate cements (GPCs) have exhibited potential as bone cements. This study investigates the effect of substituting TiO2 for SiO2 in the glass phase and the subsequent effect on cement rheology, mechanical properties, ion release and antibacterial properties. Glass characterization revealed a reduction in glass transition temperature (T(g)) from 685 to 669 °C with the addition of 6 mol % TiO2 (AT-2). Magic angle spinning nuclear magnetic resonance (MAS-NMR) revealed a shift from -81 ppm to -76 pmm when comparing a Control glass to AT-2, indicating de-polymerization of the Si network. The incorporation of TiO2 also increased the working time (T(w)) from 19 to 61 s and setting time (T(s)) from 70 to 427 s. The maximum compressive strength (σ(c)) increased from 64 to 85 MPa. Ion release studies determined that the addition of Ti to the glass reduced the release of zinc, calcium and strontium ions, with low concentrations of titanium being released. Antibacterial testing in E. coli resulted in greater bactericidal effects when tested in aqueous broth for both titanium containing cements.

Comparison of a SiO(2)-CaO-ZnO-SrO glass polyalkenoate cement to commercial dental materials: glass structure and physical properties.

Glass polyalkenoate cements (GPCs) have previously been considered for orthopedic applications. A Zn-GPC (BT 101) was compared to commercial GPCs (Fuji IX and Ketac Molar) which have a setting chemistry analogous to BT 101. Handling properties (working, T (w) and setting, T (s) times) for BT 101 were shorter than the commercial GPCs. BT 101 also had a higher setting exotherm (S (x) -34 °C) than the commercial GPCs (29 °C). The maximum strengths for BT 101, Fuji IX, and Ketac Molar were 75, 238, and 216 MPa (compressive, σ (c)), and 34, 54, and 62 MPa (biaxial flexural strengths, σ (f)), respectively. The strengths of BT 101 are more suitable for spinal applications than commercial GPCs.

Fabrication of CaO-NaO-SiO(2)/TiO (2) scaffolds for surgical applications.

A series of titanium (Ti) based glasses were formulated (0.62 SiO(2)-0.14 Na(2)O-0.24 CaO, with 0.05 mol% TiO(2) substitutions for SiO(2)) to develop glass/ceramic scaffolds for bone augmentation. Glasses were initially characterised using X-ray diffraction (XRD) and particle size analysis, where the starting materials were amorphous with 4.5 µm particles. Hot stage microscopy and high temperature XRD were used to determine the sintering temperature (~700 °C) and any crystalline phases present in this region (Na(2)Ca(3)Si(6)O(16), combeite and quartz). Hardness testing revealed that the Ti-free control (ScC-2.4 GPa) had a significantly lower hardness than the Ti-containing materials (Sc1 and Sc2 ~6.6 GPa). Optical microscopy determined pore sizes ranging from 544 to 955 µm. X-ray microtomography calculated porosity from 87 to 93 % and surface area measurements ranging from 2.5 to 3.3 SA/mm(3). Cytotoxicity testing (using mesenchymal stem cells) revealed that all materials encouraged cell proliferation, particularly the higher Ti-containing scaffolds over 24-72 h.

Gallium containing glass polyalkenoate anti-cancerous bone cements: glass characterization and physical properties.

A gallium (Ga) glass series (0.48SiO(2)-0.40ZnO-0.12CaO, with 0.08 mol% substitution for ZnO) was developed to formulate a Ga-containing Glass Polyalkenoate Cement (GPC) series. Network connectivity (NC) and X-ray Photoelectron Spectroscopy (XPS) was employed to investigate the role of Ga(3+) in the glass, where it is assumed to act as a network modifier. Ga-GPC series was formulated with E9 and E11 polyacrylic acid (PAA) at 50, 55 and 60 wt% additions. E11 working times (T(w)) ranged from 68 to 96 s (Lcon.) and 106 s for the Ga-GPCs (LGa-1 and LGa-2). Setting times (T(s)) ranged from 104 to 226 s (Lcon.) and 211 s for LGa-1 and LGa-2. Compression (σc) and biaxial flexural (σf) testing were conducted where Lcon. increased from 62 to 68 MPa, LGa-1 from 14 to 42 MPa and LGa-2 from 20 to 47 MPa in σc over 1-30 days. σf testing revealed that Lcon. increased from 29 to 42 MPa, LGa-1 from 7 to 32 MPa and LGa-2 from 12 to 36 MPa over 1-30 days.

Silver coated bioactive glass particles for wound healing applications.

Bioactive glass particles (0.42SiO(2)-0.15CaO-0.23Na(2)O-0.20ZnO) of varying size (<90 µm and 425-850 µm) were synthesized and coated with silver (Ag) to produce Ag coated particles (PAg). These were compared against the uncoated analogous particles (Pcon.). Surface area analysis determined that Ag coating of the glass particles resulted in increased the surface area from 2.90 to 9.12 m(2)/g (90 µm) and 1.09-7.71 m(2)/g (425-850 µm). Scanning electron microscopy determined that the Ag coating remained at the surface and there was little diffusion through the bulk. Antibacterial (Escherichia coli--13 mm and Staphylococcus epidermidis--12 mm) and antifungal testing (Candida albicans--7.7 mm) determined that small Ag-coated glass particles exhibited the largest inhibition zones compared to uncoated particles. pH analysis determined an overall higher pH consider in the smaller particles, where after 24 h the large uncoated and Ag coated particles were 8.27 and 8.74 respectively, while the smaller uncoated and Ag coated particles attained pH values of 9.63 and 9.35 respectively.

The bioactivity and ion release of titanium-containing glass polyalkenoate cements for medical applications.

The ion release profiles and bioactivity of a series of Ti containing glass polyalkenoate cements. Characterization revealed each material to be amorphous with a T(g) in the region of 650-660°C. The network connectivity decreased (1.83-1.35) with the addition of TiO(2) which was also evident with analysis by X-ray photoelectron spectroscopy. Ion release from cements were determined using atomic absorption spectroscopy for zinc (Zn(2+)), calcium (Ca(2+)), strontium (Sr(2+)), Silica (Si(4+)) and titanium (Ti(4+)). Ions such as Zn(2+) (0.1-2.0 mg/l), Ca(2+) (2.0-8.3 mg/l,) Sr(2+) (0.1-3.9 mg/l), and Si(4+) (14-90 mg/l) were tested over 1-30 days. No Ti(4+) release was detected. Simulated body fluid revealed a CaP surface layer on each cement while cell culture testing of cement liquid extracts with TW-Z (5 mol% TiO(2)) produced the highest cell viability (161%) after 30 days. Direct contact testing of discs resulted in a decrease in cell viability of the each cement tested.

The effect of ionic dissolution products of Ca-Sr-Na-Zn-Si bioactive glass on in vitro cytocompatibility.

Many commercial bone grafts cannot regenerate healthy bone in place of diseased bone. Bioactive glasses have received much attention in this regard due to the ability of their ionic dissolution products to promote cell proliferation, cell differentiation and activate gene expression. Through the incorporation of certain ions, bioactive glasses can become therapeutic for specific pathological situations. Calcium-strontium-sodium-zinc-silicate glass bone grafts have been shown to release therapeutic levels of zinc and strontium, however the in vitro compatibility of these materials is yet to be reported. In this study, the in vitro cytocompatibility of three different calcium-strontium-sodium-zinc-silicate glasses was examined as a function of their ion release profiles, using Novabone® bioglass as a commercial comparison. Experimental compositions were shown to release Si(4+) ranging from 1 to 81 ppm over 30 days; comparable or enhanced release in comparison to Novabone. The maximum Ca(2+) release detected for experimental compositions was 9.1 ppm, below that reported to stimulate osteoblasts. Sr(2+) release was within known therapeutic ranges, and Zn(2+) release ranged from 0.5 to 1.4 ppm, below reported cytotoxic levels. All examined glass compositions show equivalent or enhanced in vitro compatibility in comparison to Novabone. Cells exposed to BT112 ionic products showed enhanced cell viabilities indicating cell proliferation was induced. The ion release profiles suggest this effect was due to a synergistic interaction between certain combinations and concentrations of ions. Overall, results indicate that the calcium-strontium-sodium-zinc-silicate glass compositions show equivalent or even enhanced in vitro compatibility compared to Novabone®.

A spectroscopic investigation into the setting and mechanical properties of titanium containing glass polyalkenoate cements.

Titanium (Ti) implants are extensively used in a number of biomedical and dental applications. This work introduces Ti into the glass phase of a zinc based glass polyalkenoate cement (GPC) and investigates changes in handling and mechanical properties considering two molecular weight polyacrylic acids (PAA), E9 and E11. Considering the handling properties, the working time (T (w)) increased from 50 s(E9), 32 s(E11) (BT 101, Ti-free) to 169 s(E9), 74 s(E11) with TW-Z (highest Ti content), respectively. The setting time (T (s)) increased from 76 s(E9), 47 s(E11) (BT 101) to 303 s(E9), 232 s(E11) with TW-Z, respectively. Ti was also found to have a significant increase on both compressive (sigma (c)) and biaxial flexural strength (sigma (f)), where sigma (c) increased from 36 MPa(E9), 56 MPa(E11) (BT 101) to 56 MPa(E9) and 70 MPa(E11) with TW-Z respectfully. sigma (f) also increased from 11 MPa(E9), 22 MPa(E11) (BT 101) to 22 MPa(E9) and 77 MPa(E11) with TW-Z, respectively. No increase in mechanical properties was evident with respect to maturation. Raman Spectroscopy was employed to investigate changes in glass structure and the setting of the cements with. This revealed increased glass network disruption with increasing TiO(2) content and matured cement setting with TW-Z as compared to the control BT 101. FT-IR was then employed to investigate any additional setting mechanism and changes with time. Spectroscopy determined that Ca(2+)/Sr(2+)PAA complexes are primarily responsible for the setting and mechanical strength with no changes occurring over time.

Antibacterial properties of a tri-sodium citrate modified glass polyalkenoate cement.

Primary deep infection following joint replacement surgery accounts for 7% of all revisions. Glass polyalkenoate cements (GPCs) have previously been shown to exhibit antibacterial properties. The present study had two objectives. The first was to determine if addition of tri-sodium citrate (TSC) to the powder phase of an Al-free GPC (0.04 SrO-0.12 CaO-0.36 ZnO-0.48 SiO2, by mole fraction) enhanced the resultant cement's antibacterial properties against three strains of bacteria that are commonly found in periprosthetic sites following total joint replacements (TJRs); namely, E. coli, B. fragilis, and S. epidermidis. Four cement sets were prepared, which contained 0 wt% TSC (control), 5 wt% TSC, 10 wt% TSC, and 15 wt% TSC. All the TSC-modified cements were found to exhibit large inhibition zones against all the bacterial strains, especially the cement containing 15 wt% TSC against E. coli. The antibacterial properties of the TSC containing GPCs are attributed to the release of Zn and Na ions from the cements and the presence of the TSC. The second objective was to investigate if, when a modified GPC is embedded in a bovine bone model, ionic transfer occurs. It was found that Zn ions migrated from the cement to the surrounding bone, particularly at the cement-bone interface. This is a desirable outcome as Zn ions are known to play a vital role in both bone metabolism and the regeneration of healthy bone. The present results point to the potential clinical benefits of using TSC-modified GPCs in TJRs.

Zinc-based glass polyalkenoate cements with improved setting times and mechanical properties.

The suitability of glass polyalkenoate cements (GPCs) for skeletal applications is limited by the presence, in the glass phase, of the aluminium ion (Al3+), a neurotoxin. The zinc ion (Zn2+), a bacteriocide, has been incorporated into aluminium-free GPCs based on zinc silicate glasses. However, these GPCs have considerably shorter working times and poorer mechanical properties than their Al3+-containing counterparts. Based on results for calcium phosphate cements, there is an indication that mixing a GPC with an organic compound, tricalcium citrate (TSC), may lead to cements with improved rheological and mechanical properties. We developed a range of Zn-based GPCs and determined their working times (Tw), setting times (Ts), compressive strength (CS) and biaxial flexural strengths (BFS). A GPC composed of 1g of a calcium-zinc silicate glass (BT100) mixed with a 50wt.% aqueous solution on polyacrylic acid (coded E9, Mw 80,800) at a powder liquid ratio of 2:1.5 exhibited the best combination of Tw, Ts, CS and BFS. We also found that the addition of TSC (over the range 5-15wt.%) to a GPC led to significant increases in both Tw (from 40+/-3 to 100+/-4s) and Ts (from 70+/-2 to 3000+/-4s) accompanied by changes in both CS and BFS that were affected by the duration of the aging time of the specimens in distilled water (for example, after aging for 7 days CS dropped from 62+/-2 to 17+/-1MPa, while after aging for 30 days, BFS increased 27+/-6 to 31+/-7MPa and then dropped to 17+/-1MPa). Future modification and characterization of the examined GPCs are needed before they may be considered as candidates for orthopaedic applications.