Effect of high concentration nano-hydroxyapatite serum on shear bond strength of metal brackets following three different enamel surface preparation methods: An in vitro study.

OBJECTIVE: White spot lesion (WSL) is one of the most important complications of fixed orthodontic treatment. Many methods have been studied to prevent this problem. This study is aimed to investigate the effect of high concentration nano-hydroxyapatite (nHAP) on shear bond strength (SBS) of metal brackets and Adhesive Remnant Index (ARI) score in different preparation methods. MATERIAL AND METHODS: Sixty human premolars, which were extracted for orthodontic reasons were included in this in vitro study. The teeth were randomly divided into 4 groups of 15 each: one control group and three nHAP groups. After applying nHAP for 2 to 3 minutes daily for 10 days, the groups 2 to 4 underwent sandblasting using 50µm aluminium oxide and 30 seconds etching, 60 and 30 seconds etching, respectively, and the brackets were then bonded to the teeth. After debonding, SBS and ARI scores were recorded. Data were analysed using the ANOVA test and posthoc test for pairwise comparisons. RESULTS: No significant difference was observed in SBS between the control group and the nHAP groups. The sandblasted teeth showed significantly higher SBS than the 30 seconds etching after nHAP application (P=0.02). The teeth etched for 60 seconds showed a significantly higher ARI score than the 30 seconds etched teeth with (P=0.003) or without (P<0.001) nHAP application. CONCLUSIONS: The use of nHAP before bracket bonding can be considered as a caries preventive method since it did not compromise the SBS. Sixty seconds etching is recommended for less likely damage to the enamel after debonding.

A phase 1b randomized, placebo-controlled clinical trial with SNF472 in haemodialysis patients.

AIMS: SNF472 is a calcification inhibitor that is being studied as a novel treatment for calciphylaxis and cardiovascular calcification (CVC). A first study showed acceptable safety and tolerability in a single ascending dose administration in healthy volunteers and a single dose administration in haemodialysis (HD) patients. This study aimed to assess the safety, tolerability, and pharmacokinetics/pharmacodynamics relationship of intravenous SNF472 in HD patients in a multiple ascending dose administration trial with 5 doses tested for 1 week (3 administrations) and 1 dose tested for 4 weeks (12 administrations). METHODS: This double blind, randomized, placebo-controlled Phase 1b study investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of SNF472 after repeated administrations to HD patients for up to 28 days. A pharmacodynamic assessment was performed to evaluate the potential for SNF472 to inhibit hydroxyapatite (HAP) formation. Patients were grouped into 2 cohorts, receiving multiple ascending doses for 1 week (1 to 20 mg/kg, Cohort 1) and 1 dose of 10 mg/kg for 4 weeks (Cohort 2) of intravenous SNF472. RESULTS: Physical status, body weight, cardiorespiratory function, body temperature and laboratory parameters were in the normal range. No clinically relevant effects on heart rate or blood pressure were observed. No abnormal electrocardiogram or QTcB period were reported. The peak plasma concentration (7.6, 16.1, 46.0 and 66.9 µg/mL for 3, 5, 12.5 and 20 mg/kg, respectively) was observed at the end of the 4-hour infusion and thereafter concentrations declined rapidly with half-life between 32 and 65 min. SNF472 at 10 mg/kg inhibited dose dependently HAP crystallization in plasma samples after 28 days of treatment (78% inhibition, P < .001). CONCLUSIONS: SNF472 is safe and well tolerated in HD patients after 2 schemes: multiple ascending doses for 1 week and after repeated dosing of 10 mg/kg for 4 weeks. In both schemes, SNF472 inhibits the induction of HAP crystallization. These results provide support for the use of SNF472 as a novel treatment for CVC in end-stage renal disease.

Acute and 3-month effects of microcrystalline hydroxyapatite, calcium citrate and calcium carbonate on serum calcium and markers of bone turnover: a randomised controlled trial in postmenopausal women.

Ca supplements are used for bone health; however, they have been associated with increased cardiovascular risk, which may relate to their acute effects on serum Ca concentrations. Microcrystalline hydroxyapatite (MCH) could affect serum Ca concentrations less than conventional Ca supplements, but its effects on bone turnover are unclear. In the present study, we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca, phosphate, parathyroid hormone and bone turnover markers. We randomised 100 women (mean age 71 years) to 1 g/d of Ca as citrate or carbonate (citrate-carbonate), one of two MCH preparations, or a placebo. Blood was sampled for 8 h after the first dose, and after 3 months of daily supplementation. To determine whether the acute effects changed over time, eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months. There were no differences between the citrate and carbonate groups, or between the two MCH groups, so their results were pooled. The citrate-carbonate dose increased ionised and total Ca concentrations for up to 8 h, and this was not diminished after 3 months. MCH increased ionised Ca concentrations less than the citrate-carbonate dose; however, it raised the concentrations of phosphate and the Ca-phosphate product. The citrate-carbonate and MCH doses produced comparable decreases in bone resorption (measured as serum C-telopeptide (CTX)) over 8 h and bone turnover (CTX and procollagen type-I N-terminal propeptide) at 3 months. These findings suggest that Ca preparations, in general, produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover.

Biological evaluation of zirconia/PEG hybrid materials synthesized via sol-gel technique.

The objective of the following study has been the synthesis via sol-gel and the characterization of novel organic-inorganic hybrid materials to be used in biomedical field. The prepared materials consist of an inorganic zirconia matrix containing as organic component the polyethylene glycol (PEG), a water-soluble polymer used in medical and pharmaceutical fields. Various hybrids have been synthesized changing the molar ratio between the organic and inorganic parts. Fourier transform spectroscopy suggests that the structure of the interpenetrating network is realized by hydrogen bonds between the Zr-OH group in the sol-gel intermediate species and both the terminal alcoholic group and ethereal oxygen atoms in the repeating units of polymer The amorphous nature of the gels has been ascertained by X-ray diffraction analysis. The morphology observation has been carried out by using the Scanning Electron Microscope and has confirmed that the obtained materials are nanostructurated hybrids. The bioactivity of the synthesized system has been shown by the formation of a hydroxyapatite layer on the surface of samples soaked in a fluid simulating the human blood plasma. The potential biocompatibility of hybrids has been assessed as performing indirect MTT cytotoxicity assay towards 3T3 cell line at 24, 48, and 72 h exposure times.

Supersaturation of body fluids, plasma and urine, with respect to biological hydroxyapatite.

Supersaturation of body fluids, specifically of plasma and urine, with respect to biological hydroxyapatite was evaluated taking into account calcium complexation, fraction of total phosphorus present as hydrogen phosphate ions, solubility of carbonated hydroxyapatite and the size dependency of equilibrium solubility. Plasma is always supersaturated with respect to apatitic solid phase and thus calcific deposits are formed unless a sufficient quantity of potent inhibitors is present. When urinary pH is lower than 6.3 for normal urine hydroxyapatite cannot appear in renal stones, at higher pH apatitic renal stones can be formed. Predictions based on supersaturation calculated for different conditions correspond well with clinical observations.

In vitro bioactive behavior of hydroxylapatite-coated porous Al(2)O(3).

To produce bioactive materials for bone substitutes, two major deposition methods, suspension method and thermal deposition method, were employed to develop bioactive, mechanically strong, and porous ceramics. Hydroxylapatite (HA) has been uniformly coated onto inner pore surfaces of reticulated alumina substrates. It has been found that the in vitro bioactivity of HA coatings was affected by both structural crystallinity and specific surface area. Well-crystallized HA heat-treated at high temperatures has resulted in reduced bioactivity. The bio-reaction rate was found to increase with the surface area of HA. We have found that the stability of the well-crystallized HA is associated with the high driving force required for the formation of hydroxy-carbonate apatite (HCA) phase.

Synthesis of biomimetic Ca-hydroxyapatite powders at 37 degrees C in synthetic body fluids.

An important inorganic phase for synthetic bone applications, calcium hydroxyapatite (HA, Ca10(PO4)6(OH)2), was prepared as a nano-sized (approximately 50 nm), homogeneous and high-purity ceramic powder from calcium nitrate tetrahydrate and diammonium hydrogen phosphate salts dissolved in modified synthetic body fluid (SBF) solutions at 37 degrees C and pH of 7.4 using a novel chemical precipitation technique. The synthesized precursors were found to easily reach a phase purity >99% after 6 h of calcination in air atmosphere at 90 degrees C, following oven drying at 80 degrees C. There was observed, surprisingly, no decomposition of HA into the undesired beta-TCP phase even after heating at 1,600 degrees C in air for 6 h. This observation showed the superior high-temperature stability of such 'biomimetic' HA powders as compared to those reported in previous studies. The former powders were also found to contain trace amounts of Na and Mg ions, originating from the use of SBF solutions instead of pure water during their synthesis. Characterization and chemical analysis of the synthesized powders were performed by X-ray powder diffraction, energy-dispersive X-ray spectroscopy, Fourier-transform infra-red spectroscopy, scanning electron microscopy, and inductively coupled plasma atomic emission spectroscopy.

Polyethyleneglycol-stabilized manganese-substituted hydroxylapatite as a potential contrast agent for magnetic resonance imaging: particle stability in biologic fluids.

RATIONALE AND OBJECTIVES: Polymer-stabilized manganese(II)-substituted hydroxylapatite (MnHA) has been investigated as a particulate contrast agent for magnetic resonance imaging. The MnHA core requires a polymer coating to retard opsonization, thereby prolonging its systemic persistence. Therefore, the aim of this study was to assess the stability of various formulations in biologic media in vitro. METHODS: Polyethyleneglycol-coated manganese(II)-substituted hydroxylapatite particles were studied in bovine plasma as a function of the concentration of polymer in the formulation. Particle sizing techniques and nuclear magnetic resonance proton relaxometry were used to evaluate both in vitro and in vivo stability. RESULTS: A small-sized particle (approximately 10 nm diameter) that is stable in bovine plasma and rabbit whole blood was formed in formulations with high amounts of polymer concentration. In formulations with low amounts of polymer concentration, larger-sized particles (approximately 100 nm diameter) were present along with the small-sized population. The larger particles de-aggregated into the small-size particle distribution on dispersion in bovine plasma and rabbit whole blood. CONCLUSIONS: Ultrasmall particles with high surface coat were stable in plasma, whereas larger aggregates de-aggregated. Unlike Mn2+, the interaction of polyethyleneglycol-stabilized manganese(II)-substituted hydroxylapatite with plasma proteins was weak.

Serum-hydroxyapatite interaction in vitro.

In a project to develop hydroxyapatites for bone replacement, biological and synthetic types were prepared at 600 degrees C, ground to 300-600 microns and immersed in a pooled human serum for periods up to 1 month at 4 degrees C to assess material interaction. It was found that the levels of calcium in the serum were reduced at 6 h immersion, followed by an increase to reach maximum at 48 h and then stability up to 1 month. Phosphorus levels showed the opposite behaviour. Both apatites showed similar trends, although higher values were recorded for the synthetic type, suggesting higher activity. Infrared spectral analysis complemented the biochemical values, where the optical densities (O.D.) of phosphate groups were reduced, reflecting the increased phosphorus in serum and denoting leaching. Also, O.D. values of both CO3(2-) and OH- groups were reduced at 10 h, then returned to original levels. Scanning electron microscopy revealed a spongy appearance parallel with reduced O.D. and higher levels of serum Ca2+. At longer periods (48 h) the concentric needles of hydroxyapatite are clearly shown to be deposited on biological apatite. Differences in responses were attributed to their original crystalline structure assessed by X-ray diffraction analysis, as well as pore analysis using a mercury porosimeter.