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. © 2013 Springer Science+Business Media New York

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-Na2O-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 (Ca2+) release presented a significant change at each time period and was also composition dependent, where a reduction in Ca2+ release is observed with an increase in TiO2 concentration. Silica (Si4+) release did not present any clear trends while no titanium (Ti4+) 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

Ploidy variation in Kluyveromyces marxianus separates dairy and non-dairy isolates

Kluyveromyces marxianus is traditionally associated with fermented dairy products, but can also be isolated from diverse non-dairy environments. Because of thermotolerance, rapid growth and other traits, many different strains are being developed for food and industrial applications but there is, as yet, little understanding of the genetic diversity or population genetics of this species. K. marxianus shows a high level of phenotypic variation but the only phenotype that has been clearly linked to a genetic polymorphism is lactose utilisation, which is controlled by variation in the LAC12 gene. The genomes of several strains have been sequenced in recent years and, in this study, we sequenced a further nine strains fromdifferent origins. Analysis of the Single Nucleotide Polymorphisms (SNPs) in 14 strains was carried out to examine genome structure and genetic diversity. SNP diversity in K. marxianus is relatively high, with up to 3% DNA sequence divergence between alleles. It was found that the isolates include haploid, diploid, and triploid strains, as shown by both SNP analysis and flow cytometry. Diploids and triploids contain long genomic tracts showing loss of heterozygosity (LOH). All six isolates from dairy environments were diploid or triploid, whereas 6 out 7 isolates from non-dairy environment were haploid. This also correlated with the presence of functional LAC12 alleles only in dairy haplotypes. The diploids were hybrids between a non-dairy and a dairy haplotype, whereas triploids included three copies of a dairy haplotype

AB012. Transcriptional and chromatin profiling reveals the molecular architecture and druggable vulnerabilities of thymic epithelial tumors (TETs)

Thymic epithelial tumors (TETs) have been profiled to the present moment mainly through several analyses of FFPE samples. Despite the leap forward brought by the TCGA, several questions remain still unsolved. Among these, TETs are characterized by a strong component of immune infiltrate which makes the transcriptomic analyses conducted so far scarcely interpretable to profile stromal subpopulations constitutive of the tumor. Furthermore, rarely correspondent healthy tissue is available due to the lipomatous atrophy of aged thymi. Therefore, the recent report of (I) isolation, (II) propagation (III) and characterization of human thymic epithelial cells (TECs) and their capacity to reconstitute the functional organ ex vivo and in vivo, represents a novel approach to study the biology of both healthy and neoplastic thymi. Human thymic biopsies (both healthy and neoplastic) were digested and plated on a lethally irradiated murine feeder layer. Both RNA-Seq and CUTANDTAG were performed on cultivated TECs at different passages. Cultured TECs were injected with human thymic interstitial cells into rat decellularized scaffolds and cultivated for 10–12 days. sc-RNA Seq is currently being performed on both healthy and neoplastic thymic mini-organs and their correspondent primary tissues. Here show that we successfully cultivated a cohort of 21 clonogenic TECs in vitro including adult neoplastic TECs, their non-tumoral counterpart and pediatric TECs. We show that at the transcriptome level each class of TECs clusters independently and that neoplastic TECs belong to the same cloud independently from thymoma histotype. Around 1,400 differentially expressed genes (DEGs) can be found when comparing adult neoplastic and non-neoplastic counterpart, among which around 70 are transcription factors. Importantly, we prove for the first time that clonogenic TECs derived from TETs can repopulate a decellularized rat scaffold and recreate a 3D architecture mimicking the primary tumor. This work demonstrates that this culture system allows the expansion of clonogenic TECs from both tumor samples and their non-tumoral counterpart. Those cells, when transplanted into decellularized thymi, reproduce the architecture of the primary tissue, showing that TETs contain progenitor/stem epithelial cells. We are currently characterizing TECs at the transcriptomic and epigenomic level with aim of identifying new druggable targets prior to clinical trials

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

A glass series [xSiO(2[-y])center dot 0.36ZnO center dot 0.17Na(2)O center dot 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 m(2)/g (control), to 0.53-1.85 m(2)/g (AU-1), and 0.20-1.11 m(2)/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)

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. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav

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