Resin tags formation by modified Renewal MI formulations in a carious dentine model.

Objectives: To determine which components in a new restorative material (Renewal MI) improve its ability to form resin tags within demineralized dentine. Methods: Varied components included polylysine (PLS), monocalcium phosphate (MCP), powder to liquid ratio (PLR), 4-methacryloyloxyethyl trimellitate anhydride (4META), and polypropylene glycol dimethacrylate (PPGDMA). Urethane dimethacrylate (UDMA), containing PPGDMA (24 wt%) and 4META (3 wt%), was mixed with glass filler with MCP (8 wt%) and PLS (5 wt%). PLR was 3:1 or 5:1. Reducing MCP and/or PLS to 4 and 2 wt% respectively or fully removing MCP, PLS, 4META or PPGDMA gave 16 formulations in total. Renewal MI, Z250 (with or without Scotchbond Universal adhesive) and Activa were used as commercial comparators. Collagen discs were obtained by totally demineralizing 2 mm thick, human, premolar, coronal dentine discs by immersion in formic acid (4M) for 48 h. The restorative materials were then applied on top (n = 3), before dissolving the collagen in sodium hypochlorite (15%). SEM/EDX was employed to determine resin tags length, composition, and surface coverage. Results: Tags were >400, 20 and 200 µm and covered 62, 55 and 39% of the adhesion interface for Renewal MI, Scotchbond and Activa, respectively. With experimental formulations, they were 200 and >400 µm long with high vs. low PLR and composed primarily of polymerized monomers. Percentages of the adhesion interface covered varied between 35 and 84%. Reducing PLS or MCP caused a decline in coverage that was linear with their concentrations. Reducing MCP had lesser effect when PLS or PLR were low. Removal of 4META caused a greater reduction in coverage than PPGDMA removal. Conclusion: PLS, MCP, 4META, PPGDMA and low PLR together enhance Renewal MI tags formation in, and thereby sealing of, demineralized dentine.

Polymerization kinetics stability, volumetric changes, apatite precipitation, strontium release and fatigue of novel bone composites for vertebroplasty.

PURPOSE: The aim was to determine effects of diluent monomer and monocalcium phosphate monohydrate (MCPM) on polymerization kinetics and volumetric stability, apatite precipitation, strontium release and fatigue of novel dual-paste composites for vertebroplasty. MATERIALS AND METHODS: Polypropylene (PPGDMA) or triethylene (TEGDMA) glycol dimethacrylates (25 wt%) diluents were combined with urethane dimethacrylate (70 wt%) and hydroxyethyl methacrylate (5 wt%). 70 wt% filler containing glass particles, glass fibers (20 wt%) and polylysine (5 wt%) was added. Benzoyl peroxide and MCPM (10 or 20 wt%) or N-tolyglycine glycidyl methacrylate and tristrontium phosphate (15 wt%) were included to give initiator or activator pastes. Commercial PMMA (Simplex) and bone composite (Cortoss) were used for comparison. ATR-FTIR was used to determine thermal activated polymerization kinetics of initiator pastes at 50-80°C. Paste stability, following storage at 4-37°C, was assessed visually or through mixed paste polymerization kinetics at 25°C. Polymerization shrinkage and heat generation were calculated from final monomer conversions. Subsequent expansion and surface apatite precipitation in simulated body fluid (SBF) were assessed gravimetrically and via SEM. Strontium release into water was assessed using ICP-MS. Biaxial flexural strength (BFS) and fatigue properties were determined at 37°C after 4 weeks in SBF. RESULTS: Polymerization profiles all exhibited an inhibition time before polymerization as predicted by free radical polymerization mechanisms. Initiator paste inhibition times and maximum reaction rates were described well by Arrhenius plots. Plot extrapolation, however, underestimated lower temperature paste stability. Replacement of TEGDMA by PPGDMA, enhanced paste stability, final monomer conversion, water-sorption induced expansion and strontium release but reduced polymerization shrinkage and heat generation. Increasing MCPM level enhanced volume expansion, surface apatite precipitation and strontium release. Although the experimental composite flexural strengths were lower compared to those of commercially available Simplex, the extrapolated low load fatigue lives of all materials were comparable. CONCLUSIONS: Increased inhibition times at high temperature give longer predicted shelf-life whilst stability of mixed paste inhibition times is important for consistent clinical application. Increased volumetric stability, strontium release and apatite formation should encourage bone integration. Replacing TEGDMA by PPGDMA and increasing MCPM could therefore increase suitability of the above novel bone composites for vertebroplasty. Long fatigue lives of the composites may also ensure long-term durability of the materials.

Alpha-1 Antitrypsin Inhibits ATP-Mediated Release of Interleukin-1ß via CD36 and Nicotinic Acetylcholine Receptors.

While interleukin (IL)-1ß is a potent pro-inflammatory cytokine involved in host defense, high levels can cause life-threatening sterile inflammation including systemic inflammatory response syndrome. Hence, the control of IL-1ß secretion is of outstanding biomedical importance. In response to a first inflammatory stimulus such as lipopolysaccharide, pro-IL-1ß is synthesized as a cytoplasmic inactive pro-form. Extracellular ATP originating from injured cells is a prototypical second signal for inflammasome-dependent maturation and release of IL-1ß. The human anti-protease alpha-1 antitrypsin (AAT) and IL-1ß regulate each other via mechanisms that are only partially understood. Here, we demonstrate that physiological concentrations of AAT efficiently inhibit ATP-induced release of IL-1ß from primary human blood mononuclear cells, monocytic U937 cells, and rat lung tissue, whereas ATP-independent IL-1ß release is not impaired. Both, native and oxidized AAT are active, suggesting that the inhibition of IL-1ß release is independent of the anti-elastase activity of AAT. Signaling of AAT in monocytic cells involves the lipid scavenger receptor CD36, calcium-independent phospholipase A2ß, and the release of a small soluble mediator. This mediator leads to the activation of nicotinic acetylcholine receptors, which efficiently inhibit ATP-induced P2X7 receptor activation and inflammasome assembly. We suggest that AAT controls ATP-induced IL-1ß release from human mononuclear blood cells by a novel triple-membrane-passing signaling pathway. This pathway may have clinical implications for the prevention of sterile pulmonary and systemic inflammation.

Monomer conversion, dimensional stability, strength, modulus, surface apatite precipitation and wear of novel, reactive calcium phosphate and polylysine-containing dental composites.

PURPOSE: The aim was to assess monomer conversion, dimensional stability, flexural strength / modulus, surface apatite precipitation and wear of mono / tri calcium phosphate (CaP) and polylysine (PLS)-containing dental composites. These were formulated using a new, high molecular weight, fluid monomer phase that requires no polymerisation activator. MATERIALS AND METHODS: Urethane and Polypropylene Glycol Dimethacrylates were combined with low levels of an adhesion promoting monomer and a light activated initiator. This liquid was mixed with a hybrid glass containing either 10 wt% CaP and 1 wt% PLS (F1) or 20 wt% CaP and 2 wt% PLS (F2). Powder to liquid mass ratio was 5:1. Commercial controls included Gradia Direct Posterior (GD) and Filtek Z250 (FZ). Monomer conversion and polymerisation shrinkage were calculated using Fourier Transform Infrared (FTIR). Subsequent volume increases in water over 7 weeks were determined using gravimetric studies. Biaxial flexural strength (BFS) / modulus (BFM) reduction and surface apatite precipitation upon 1 and 4 weeks immersion in water versus simulated body fluid (SBF) were assessed using a mechanical testing frame and scanning electron microscope (SEM). Mass / volume loss and surface roughness (Ra) following 7 weeks water immersion and subsequent accelerated tooth-brush abrasion were examined using gravimetric studies and profilometer. RESULTS: F1 and F2 exhibited much higher monomer conversion (72%) than FZ (54%) and low calculated polymerization shrinkage (2.2 vol%). Final hygroscopic expansions decreased in the order; F2 (3.5 vol%) > F1 (1.8 vol%) ~ Z250 (1.6 vol%) > Gradia (1.0 vol%). BFS and BFM were unaffected by storage medium type. Average BFS / BFM upon 4 weeks immersion reduced from 144 MPa / 8 GPa to 107 MPa / 5 GPa for F1 and 105 MPa / 6 GPa to 82 MPa / 4 GPa for F2. Much of this change was observed in the first week of immersion when water sorption rate was high. Surface apatite layers were incomplete at 1 week, but around 2 and 15 micron thick for F1 and F2 respectively following 4 weeks in SBF. Mass and volume loss following wear were equal. Average results for F1 (0.5%), F2 (0.7%), and FZ (0.5%) were comparable but lower than that of GD (1%). Ra, however, decreased in the order; F1 (15 µm) > F2 (11 µm) > GD (9 µm) > FZ (5 µm). CONCLUSIONS: High monomer conversion in combination with large monomer size and lack of amine activator should improve cytocompatibility of the new composites. High monomer molecular weight and powder content enables low polymerisation shrinkage despite high conversion. Increasing active filler provides enhanced swelling to balance shrinkage, which, in combination with greater surface apatite precipitation, may help seal gaps and reduce bacterial microleakage. High monomer conversion also ensures competitive mechanical / wear characteristics despite enhanced water sorption. Furthermore, increased active filler could help reduce surface roughness upon wear.