A. Coughlan

Experimental composite guidance conduits for peripheral nerve repair: An evaluation of ion release

Poly (lactide-co-glycolide) (PLGA) - Pluronic F127 - glass composites have demonstrated excellent potential, from the perspective of controlled mechanical properties and cytocompatibility, for peripheral nerve regeneration. In addition to controlling the mechanical properties and cytotoxicity for such composite devices, the glass component may mediate specific responses upon implantation via degradation in the physiological environment and release of constituent elements. However, research focused on quantifying the release levels of such therapeutic ions from these experimental medical devices has been limited. To redress the balance, this paper explores the ion release profiles for Si(4+), Ca(2+), Na(+), Zn(2+), and Ce(4+) from experimental composite nerve guidance conduits (CNGC) comprising PLGA (at 12.5, and 20 wt.%), F127 (at 0, 2.5 and 5 wt.%) and various loadings of Si-Ca-Na-Zn-Ce glass (at 20 and 40 wt.%) for incubation periods of up to 28 days. The concentration of each ion, at various time points, was determined using Inductively Coupled Plasma-Atomic Emission Spectrometry (Perkin Elmer Optima 3000). It was observed that the Si(4+), Na(+), Ca(2+), Zn(2+) release from CNGCs in this study ranged from 0.22 to 6.477 ppm, 2.307 to 3.277 ppm, 40 to 119 ppm, and 45 to 51 ppm, respectively. The Ce(4+) concentrations were under the minimum detection limits for the ICP instrument utilized. The results indicate that the ion release levels may be appropriate to mediate therapeutic effects with respect to peripheral nerve regeneration. The data generated in this paper provides requisite evidence to optimize composition for pre-clinical evaluation of the experimental composite.

Investigating the solubility and cytocompatibility of CaO–Na2O–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.

Drug-eluting cements for hard tissue repair: A comparative study using vancomycin and RNPA1000 to inhibit growth of Staphylococcus aureus

Bone cement used in orthopaedic applications can become colonized with bacterial biofilms, resulting in severe medical complications. Consequently, bone cements are often loaded with antibiotics in an effort to prevent bacterial colonization. However, current formulations may not release antibiotics into the environment at sufficient and sustained concentrations required to impede bacterial growth or may be incompatible with antibiotics that are effective against the colonizing organism. Thus, new cement formulation options are needed. This report describes the performance of a novel SiO2-TiO2-ZnO-CaO-SrO-based glass polyalkenoate cement as a carrier of antimicrobials active against Staphylococcus aureus, the predominant cause of orthopaedic biofilm-associated infections. The antibiotic vancomycin and a novel Staphylococcus aureus RnpA inhibitor under pre-clinical development, RNPA1000, were included in these studies. Rheological testing characterized the workability of the glass polyalkenoate cement over a range of powder-to-liquid ratios and polyacrylic acid concentrations and revealed that the most suitable powder-to-liquid ratio was 2/1.25 with 40 wt& polyacrylic acid. Loading glass polyalkenoate cement with either 20–30& RNPA1000 or vancomycin prevented bacterial growth. However, longer incubations allowed for Staphylococcus aureus colonies to form near the vancomycin-infused cement, indicating that vancomycin may not be suitable for long-term biofilm inhibition in comparison to RNPA1000. Scanning electron microscopy and energy-dispersive X-ray analyses confirmed successful incorporation RNPA1000 into the cement matrix and were indicative of its slow release. These studies establish a drug-eluting formulation of glass polyalkenoate cement with great potential in orthopaedic implants that incorporates known antibiotics as well as RNPA1000 to prevent growth of the dangerous pathogen Staphylococcus aureus.

Characterization and antibacterial efficacy of silver-coated Ca-Na-Zn-Si/Ti glasses.

A glass series [xSiO2[−y]·0.36ZnO·0.17Na2O·0.05CaO (starting at x = 0.50, y = 0.08 TiO2)] was formulated with TiO2 substituting SiO2. Each glass/silver-coated glass was characterized using X-ray diffraction, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy. Surface area analysis revealed significant changes after silver coating, 0.43–0.95 m2/g (control), to 0.53–1.85 m2/g (AU-1), and 0.20–1.11 m2/g (AU-2). Ion release from uncoated glasses included sodium (0.08 mg/L), calcium (0.07 mg/L), and zinc (0.008 mg/L), where silver-coated glasses presented 0.42 mg/L (silver), 0.33 mg/L (sodium), 0.02 mg/L (calcium), and 0.01 mg/L (zinc). Ag-coated glasses presented inhibition zones of 7.75 mm (control) compared to 1.04 mm (AU-2).

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).

Preliminary Investigation of the Dissolution Behavior, Cytocompatibility, Effects of Fibrinogen Conformation and Platelet Adhesion for Radiopaque Embolic Particles

Experimental embolic particles based on a novel zinc-silicate glass system have been biologically evaluated for potential consideration in transcatheter arterial embolization procedures. In addition to controlling the cytotoxicity and haemocompatibility for such embolic particles, its glass structure may mediate specific responses via dissolution in the physiological environment. In a 120 h in-vitro dissolution study, ion release levels for silicon (Si4+), sodium (Na+), calcium (Ca2+), zinc (Zn2+), titanium (Ti4+), lanthanum (La3+), strontium (Sr2+), and magnesium (Mg2+), were found to range from 0.04 to 5.41 ppm, 0.27–2.28 ppm, 2.32–8.47 ppm, 0.16–0.20 ppm, 0.12–2.15 ppm, 0.16–0.49 ppm and 0.01–0.12 ppm, respectively for the series of glass compositions evaluated. Initial release of Zn2+ (1.93–10.40 ppm) was only evident after 120 h. All compositions showed levels of cell viabilities ranging from 61.31 ± 4.33% to 153.7 ± 1.25% at 25%–100% serial extract dilutions. The conformational state of fibrinogen, known to induce thrombi, indicated that no changes were induced with respect of the materials dissolution by-products. Furthermore, the best-in-class experimental composition showed equivalency to contour PVA in terms of inducing platelet adhesion. The data generated here provides requisite evidence to continue to in-vivo pre-clinical evaluation using the best-in-class experimental composition evaluated.

Does elevating silver content in zinc-based glass polyalkenoate cements increase their antibacterial efficacy against two common bacteria using the agar gel diffusion method?

The authors have previously shown that it is possible to incorporate silver into a soda-zinc-silicate glass and subsequently form a glass polyalkenoate cement from it. The objective of the research described herein is to determine if incremental increases in the silver content of these glass polyalkenoate cements will increase their antibacterial efficacy against gram-positive and gram-negative bacteria using the accepted spread plate method. Four glass polyalkenoate cements were formulated; three contained increasing amounts of silver incorporated into them (cements A, B, and C, containing 0.33 mol%, 0.66 mol%, and 0.99 mol% silver, respectively) and a fourth contained no silver, which acted as a control (control cement). The handling properties of the glass polyalkenoate cements were evaluated, where working times were around 2 min and setting times ranged from 1 h 17 min to 2 h 41 min. Inductively coupled plasma atomic emission spectroscopy was employed to determine silver ion release with cement maturation for up to 14 days. The majority of silver ions were released within the first 24 h, with up to 2 mg/L cumulative ion release recorded up to 14 days. The antibacterial properties of the coatings were evaluated against Staphylococcus aureus and Pseudomonas aeruginosa bacteria. The silver-glass polyalkenoate cements exhibited antibacterial effect against both bacterial strains. The maximum inhibition zones recorded against S. aureus was 14.8 mm (SD ± 1.11) and against P. aeruginosa was 20.6 mm (SD ± 0.81). Cement B had a greater antibacterial effect compared to cement A, however, cements B and C had comparable antibacterial effects after 14 days even though cement C contained 0.33 mol% more silver than B. This indicates that by increasing the silver content in these cements, the antibacterial efficacy increases to a point, but there is a threshold where further silver ion release does not increase the antibacterial effect.

Characterization of Y 2 O 3 and CeO 2 doped SiO 2 -SrO-Na 2 O glasses

Abstract The structural effects of yttrium (Y) and cerium (Ce) are investigated when substituted for sodium (Na) in a 0.52SiO2–0.24SrO–(0.24−x)Na2O–xMO (where x = 0.08; MO = Y2O3 and CeO2) glass series. Network connectivity (NC) was calculated assuming both Y and Ce can act as a network modifier (NC = 2.2) or as a network former (NC up to 2.9). Thermal analysis showed an increase in glass transition temperature (Tg) with increasing Y and Ce content, Y causing the greater increase from the control (Con) at 493∘C to 8 mol% Y (HY) at 660∘C. Vickers hardness (HV) was not significantly different between glasses. 29Si Magic Angle Spinning-Nuclear Magnetic Resonance (MAS-NMR) did not show peak shift with addition of Y, however Ce produced peak broadening and a negative shift in ppm. The addition of 4 mol% Ce in the YCe and LCe glasses shifted the peak from Con at −81.3 ppm to −82.8 ppm and −82.7 ppm respectively; while the HCe glass produced a much broader peak and a shift to −84.8 ppm. High resolution X-ray Photoelectron Spectroscopy for the O 1s spectral line showed the ratio of bridging (BO) to non-bridging oxygens (NBO), BO:NBO,was altered,where Con had a ratio of 0.7, HY decreased to 0.4 and HCe to 0.5.

Fill Volume as an Indicator of Surface Heterogeneity in Glass Vials for Parenteral Packaging

The chemical durability of glass vials for parenteral packaging is typically assessed by completely filling the vial with a medium of interest. This testing approach can mask the heterogeneous dissolution behavior of vials produced by conversion of glass tubing. In this study, the corrosion behavior of vials provided by four suppliers was evaluated as a function of fill volume. Vials were filled with incrementally increasing volumes of water for injection (WFI) up to near-maximum capacity and then autoclaved. The pH and levels of extracted ions were measured. The pH of autoclaved WFI generally increased for low fill volumes relative to pure WFI, presumably because of extraction of alkali from the heel region. The pH was found to generally decrease with increasing fill volume as the concentration of extractables was diluted. Analysis of dissolution profiles supports the altered surface chemistry of the heel region relative to the body. The results of this study demonstrate the potential limitations of conventional hydrolytic resistance tests and the susceptibility of the heel region to aqueous corrosion.

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

AbstractGlass 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.