Tranexamic acid-loaded hemostatic nanoclay microsphere frameworks.

Fast acting topical hemostatic agents play a key role in hemorrhage control. Retarding fibrinolysis is also critical in improving coagulation, thereby expanding chances of survival. The purpose of the present work was to investigate the physical properties, loading capacity and hemostatic efficacy of newly developed nanoclay microsphere frameworks (NMFs) loaded with tranexamic acid (TA), as antifibrinolytic agent. Nanoclay compositions were prepared with increasing levels of TA. Results showed that TA was successfully incorporated into the nanoclay structure and released when solvated with ethanol. Both doped and undoped NMFs significantly decreased activated partial thromboplastin time and increased clot stiffness, which was attributed to significantly thinner fibrin fibers and a denser clot structure.

Effect of crystalline phase assemblage on reliability of 3Y-TZP.

STATEMENT OF PROBLEM: Strengthening mechanisms of zirconia ceramics stabilized with 3 mol% yttria (3Y-TZP) are complex and dictated by the crystalline phase assemblage. Although their clinical performance for dental restorations has been excellent, there is evidence that framework fractures do occur and have been underreported. Meanwhile, the relationship between phase assemblage and reliability of 3Y-TZP is not properly understood. PURPOSE: The purpose of this in vitro study was to elucidate the relationship between crystalline phase assemblage and the reliability of 3Y-TZP and to calculate the associated probabilities of survival. MATERIAL AND METHODS: Disks of 3Y-TZP were prepared from cylindrical blanks and randomly assigned to 12 experimental groups (n=20 per group). Different crystalline phase assemblages were produced by either varying the sintering temperature from 1350 °C to 1600 °C and/or treating the surface by airborne-particle abrasion with 50-mm alumina particles at a pressure of 0.2 MPa for 1 minute with or without subsequent heat treatment. Crystalline phases were analyzed by standard and grazing incidence X-ray diffraction (GIXRD). The relationship between phase assemblage and reliability was determined by measuring the biaxial flexural strength (BFS) according to ISO standard 6872 and by using Weibull statistics to calculate the Weibull modulus (m), probability of survival, and maximum allowable stresses. XRD results were analyzed by ANOVA to detect statistically significant differences between groups. Adjustment for all pairwise group comparisons was made using the Tukey method (α=.05). RESULTS: Standard incidence XRD confirmed the presence of a small amount of cubic phase after sintering at 1350 °C. A cubic-derived nontransformable tetragonal t'-phase was observed at sintering temperatures of 1450 °C and above, the amount of which increased linearly. GIXRD revealed that airborne-particle abraded groups sintered at 1350 °C and 1600 °C had the highest variability in monoclinic phase fraction as a function of depth. These groups were also associated with the lowest reliability. Groups as-sintered at 1350 °C and 1600 °C had the lowest modulus (m=8.1 [0.5] and 7.0 [0.8], respectively) and probability of survival (Ps) for a maximum allowable stress of 700 MPa, while treated groups sintered at 1450 °C and 1550 °C were associated with the highest modulus (from 15.0 [1.4] to 20.9 [1.4]) and Ps (≥0.9999). The lower strength and reliability of groups sintered at 1600 °C was consistent with the presence of a significant amount of nontransformable t'-phase. The pattern of BFS results indicated that ferro-elastic domain switching was a dominant strengthening mechanism in 3Y-TZP. CONCLUSIONS: The present study first reported on the detrimental effect of the cubic-derived nontransformable t'-phase on the mechanical properties of 3Y-TZP. It was demonstrated that phase assemblage determined reliability and was directly linked to the probability of survival.

Crystalline phase evolution and thermal behavior of zirconia-lanthanum aluminate ceramics produced by surface modification.

The purpose of the present work was to investigate the effect doping with lanthanum aluminate on the phase assemblage and thermal behavior of zirconia ceramics for biomedical applications. Four compositions were prepared by a surface modification route of either conventional tetragonal zirconia (3Y-TZP) or high translucency cubic-based zirconia (5Y-PSZ) to reach a nominal composition of either 0.5 wt. % (3Y-0.5LAO and 5Y-0.5LAO) or 5 wt. % of lanthanum monoaluminate (3Y-5LAO and 5Y-5LAO). Undoped powders were used as controls. DTA and XRD analyses revealed that lanthanum dizirconate crystallized in the 934°C-936°C range, while lanthanum aluminate crystallized in the 1,056°C-1,063°C range in both types of zirconias doped at the 5% level. No second phase was found in compositions doped at the 0.5% level. The a lattice parameter and the amount of the cubic phase increased in both 3Y-5LAO and 5Y-5LAO. The microstructure of the compositions doped with 5% LAO was characterized by well distributed LAO twinned crystals and sparse needle-shaped lanthanum hexaaluminate crystals. A bimodal grain size distribution was observed in 5Y-doped compositions. This was attributed to abnormal grain growth of the cubic phase, and in line with aluminum segregation at grain boundaries and the presence of second-phase LAO crystals.

Antimicrobial efficacy of platinum-doped silver nanoparticles.

Silver nanoparticles (AgNPs) have been proposed to combat oral infection due to their efficient ionic silver (Ag+ ) release. However, concentrations required for antimicrobial efficacy may not be therapeutically viable. In this work, platinum-doped silver nanoparticles (Pt-AgNPs) were explored to evaluate their potential for enhanced Ag+ release, which could lead to enhanced antimicrobial efficacy against S. aureus, P. aeruginosa, and E. coli. AgNPs doped with 0.5, 1, and 2 mol% platinum (Pt0.5 -AgNPs, Pt1 -AgNPs, and Pt2 -AgNPs) were synthesized by a chemical reduction method. Transmission electron microscopy revealed mixed morphologies of spherical, oval, and ribbon-like nanostructures. Surface-enhanced Raman scattering revealed that the surface of Pt-AgNPs was covered with up to 93% Pt. The amount of Ag+ released increased 16.3-fold for Pt2 -AgNPs, compared to AgNPs. The initial lag phase in bacterial growth curve was prolonged for Pt-AgNPs. This is consistent with a Ag+ release profile that exhibited an initial burst followed by sustained release. Doping AgNPs with platinum significantly increased the antimicrobial efficacy against all species. Pt2 -AgNPs exhibited the lowest minimum inhibitory concentrations, followed by Pt1 -AgNPs, Pt0.5 -AgNPs, and AgNPs, respectively. Doping AgNPs with a small amount of platinum promoted the release of Ag+ , based on the sacrificial anodic effect, and subsequently enhanced their antimicrobial efficacy.

Effect of Surface Modification on In-Depth Transformations and Flexural Strength of Zirconia Ceramics.

PURPOSE: Chairside surface adjustments of zirconia dental restorations enhance the toughening stress-induced tetragonal-to-monoclinic phase transformation and domain reorientation by ferro-elastic domain switching (FDS), but also trigger subsurface damage, which could compromise long-term clinical performance. The purpose of this study was to assess the depth of phase transformation, associated FDS, and flexural strength of dental zirconia (BruxZir HT 2.0), after chairside surface treatments. MATERIALS AND METHODS: Square specimens were sectioned from CAD/CAM blocks and sintered according to manufacturer's recommendations (n = 30). They were left as-sintered (AS; control), air abraded with fine (AAF) or coarse (AAC) alumina particles, ground (G) or ground and polished (GP). Roughness was measured by profilometry. Crystalline phases were investigated by grazing incidence X-ray diffraction (GIXRD) (n = 3). GIXRD data were fit using semi-log regression protocols to assess transformation depth and extent of FDS. The mean biaxial flexural strength was measured according to ISO 6872. Subsurface damage was assessed from SEM images using a bonded polished interface configuration. Flaw distribution was assessed by Weibull analysis. Results were analyzed by Kruskal-Wallis with Tukey's adjustment for multiple comparisons (p < 0.05). RESULTS: Air-abraded and ground groups exhibited higher mean surface roughness than control. AAF group exhibited the highest flexural strength (1662.6 ± 202.6 MPa) with flaw size (5.9 ± 1.8 µm) smaller than transformation (14.5 ± 1.2 µm) or FDS depth (19.3 ± 1.1 µm), followed by GP group (1567.2 ± 209.7 MPa) with smallest FDS depth (9.3 ± 2.0 µm) and flaw size (2.6 ± 1.8 µm), but without m-phase. AAC group (1371.4 ± 147.6 MPa) had the largest flaw size (40.3 ± 20.3 µm), transformation depth (47.2 ± 3.0 µm) and FDS depth (41.2 ± 2.2 µm). G group (1357.0 ± 196.7 MPa) had the smallest transformation depth (8.6 ± 1.5 µm), and mean FDS depth (19.8 ± 3.7 µm) and flaw size (18.6 ± 3.1 µm). AAC and AAF exhibited the highest Weibull modulus (11.2 ± 0.4 and 9.8 ± 0.3 µm, respectively). CONCLUSIONS: Variations in mean biaxial flexural strength were explained by the balance between the depth of toughening mechanisms (phase transformation and FDS) and subsurface damage. AAF and GP groups were the most efficient surface adjustments in promoting the highest mean biaxial flexural strength.

Strontium-releasing fluorapatite glass-ceramic scaffolds: Structural characterization and in vivo performance.

There is increasing interest in biodegradable ceramic scaffolds for bone tissue engineering capable of in situ delivery of ionic species favoring bone formation. Strontium has been shown to be osteogenic, but strontium-containing drugs such as strontium ranelate, used in Europe for the treatment of osteoporosis, are now restricted due to clinical evidence of systemic effects. By doping fluorapatite-based glasses with strontium, we developed ceramic scaffolds with fully interconnected macroporosity and cell size similar to that of cancellous bone, that are also capable of releasing strontium. The crystallization behavior, investigated by XRD and SEM, revealed the formation of akermanite and fluorapatite at the surface of strontium-free glass-ceramic scaffolds, and strontium-substituted fluorapatite at the surface of the strontium-doped scaffolds. At 8 weeks after implantation in a rat calvarial critical size defect, scaffolds doped with the highest amount of strontium led to the highest mineral apposition rate. A significantly higher amount of newly-formed bone was found with the strontium-free glass-ceramic scaffold, and possibly linked to the presence of akermanite at the scaffold surface. We demonstrate by energy dispersive XRF analyses of skull sections that strontium was present in newly formed bone with the strontium-doped scaffolds, while a significant amount of fluorine was incorporated in newly formed bone, regardless of composition or crystallization state. STATEMENT OF SIGNIFICANCE: The present work demonstrates the in vivo action of strontium-containing glass-ceramic scaffolds. These bone graft substitutes are targeted at non load-bearing bone defects. Results show that strontium is successfully incorporated in newly formed bone. This is associated with a significantly higher Mineral Apposition Rate. The benefits of in situ release of strontium are demonstrated. The broader scientific impact of this works builds on the concept of resorbable ceramic scaffolds as reservoirs of ionic species capable of enhancing bone regeneration.

Strontium-releasing fluorapatite glass-ceramics: Crystallization behavior, microstructure, and solubility.

The purpose of this work was to investigate the effect of strontium partial replacement for calcium on the crystallization behavior, microstructure and solubility of fluorapatite glass-ceramics. Four glass compositions were prepared with increasing amounts of strontium partially replacing calcium. The crystallization behavior was analyzed by differential scanning calorimetry and X-ray diffraction (XRD). The microstructure was investigated by scanning electron microscopy. The chemical solubility was quantified according to ISO standard 10993-14. The amount of strontium released in solution after incubation in TRIS-HCl or citric acid buffer was measured by atomic absorption spectroscopy. XRD analyses revealed that partially substituted strontium-fluorapatite and strontium-åkermanite crystallized after strontium additions. The lattice cell volume of both phases increased linearly with the amount of strontium in the composition. Strontium additions led to a reduction in crystal size and an increase in crystal number density. The chemical solubility and amount of strontium released in solution increased linearly with the amount of strontium present in the composition in both TRIS-HCl and citric acid buffers. Total amounts of strontium released reached a maximum of 547 ± 80 ppm in TRIS-HCl and 1252 ± 290 ppm in citric acid buffer for the glass composition with the highest amount of strontium. For all strontium-containing compositions, the amount released in TRIS-HCl continued to increase between 70 and 120 h, indicating sustained release rather than burst release. © 2017 Wiley Periodicals, Inc. J Biomater Res Part B: 106B: 1421-1430, 2018.

Rapid vacuum sintering: A novel technique for fabricating fluorapatite ceramic scaffolds for bone tissue engineering.

Macroporous bioceramic scaffolds are often fabricated via the foam replica technique, based on polymeric foam impregnation with a glass slurry, followed by slow heat treatment to allow for drying, polymeric burnout, and sintering of the glass particles. As a consequence, the process is time consuming and complicated by concurrent crystallization of the glass, often leading to incomplete sintering. Our goal was to investigate the effect of heating rate on sintering behavior, architecture, and mechanical properties of fluorapatite-based glass and glass-ceramic scaffolds. Glass scaffolds were prepared and sintered by rapid vacuum sintering (RVS) at 785°C under vacuum at a fast heating rate (55°C/min.) or without vacuum at a slow heating rate (2°C/min.). Two additional groups were further crystallized at 775°C/1 h. XRD confirmed the presence of fluorapatite for crystallized scaffolds. All groups presented interconnected porosity with a pore size in the 500 µm range. Scaffolds produced by RVS exhibited an excellent degree of sintering while scaffolds produced by slow sintering were incompletely sintered. The mean compressive strength was significantly higher for the RVS groups (1.52 ± 0.55 and 1.72 ± 0.61 MPa) compared to the slow-sintered groups (0.54 ± 0.30 and 0.45 ± 0.26 MPa). Meanwhile, the total production time was reduced by more than 12 h by using the RVS technique. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 291-299, 2018.

Design and characterization of calcium phosphate ceramic scaffolds for bone tissue engineering.

OBJECTIVES: Our goal is to review design strategies for the fabrication of calcium phosphate ceramic scaffolds (CPS), in light of their transient role in bone tissue engineering and associated requirements for effective bone regeneration. METHODS: We examine the various design options available to meet mechanical and biological requirements of CPS and later focus on the importance of proper characterization of CPS in terms of architecture, mechanical properties and time-sensitive properties such as biodegradability. Finally, relationships between in vitro versus in vivo testing are addressed, with an attempt to highlight reliable performance predictors. RESULTS: A combinatory design strategy should be used with CPS, taking into consideration 3D architecture, adequate surface chemistry and topography, all of which are needed to promote bone formation. CPS represent the media of choice for delivery of osteogenic factors and anti-infectives. Non-osteoblast mediated mineral deposition can confound in vitro osteogenesis testing of CPS and therefore the expression of a variety of proteins or genes including collagen type I, bone sialoprotein and osteocalcin should be confirmed in addition to increased mineral content. CONCLUSIONS: CPS are a superior scaffold material for bone regeneration because they actively promote osteogenesis. Biodegradability of CPS via calcium and phosphate release represents a unique asset. Structural control of CPS at the macro, micro and nanoscale and their combination with cells and polymeric materials is likely to lead to significant developments in bone tissue engineering.

Internal fit of pressed and computer-aided design/computer-aided manufacturing ceramic crowns made from digital and conventional impressions.

STATEMENT OF PROBLEM: No studies have evaluated the internal adaptation of pressed and milled ceramic crowns made from digital impressions. PURPOSE: The purpose of this in vitro study was to evaluate the internal fit of pressed and milled ceramic crowns made from digital and conventional impressions. MATERIAL AND METHODS: Thirty polyvinyl siloxane (PVS) impressions and 30 Lava COS impressions made of a prepared dentoform tooth (master die) were fabricated. Thirty crowns were pressed in lithium disilicate (IPS e.max Press), and 30 crowns were milled from lithium disilicate blocks (IPS e.max CAD) (15/impression technique) with the E4D scanner and milling engine. The master die and the intaglio of the crowns were digitized with a 3-dimensional laser coordinate measurement machine. The digital master die and intaglio of each crown were merged. The distance between the die and the intaglio surface of the crown was measured at 3 standardized points. One-way ANOVA was used for statistical analysis (α=.05). RESULTS: One-way ANOVA revealed that the internal gap obtained from the Lava/press group (0.211 mm, ±SD 0.041) was significantly greater than that obtained from the other groups (P<.001), while no significant differences were found among PVS/press (0.111 mm ±SD 0.047), PVS/CAD/CAM (0.116 mm ±SD 0.02), and Lava/CAD/CAM (0.145 mm ±SD 0.024). CONCLUSIONS: The combination of the digital impression and pressed crown produced the least accurate internal fit.

3D and 2D marginal fit of pressed and CAD/CAM lithium disilicate crowns made from digital and conventional impressions.

PURPOSE: This in vitro study evaluated the 3D and 2D marginal fit of pressed and computer-aided-designed/computer-aided-manufactured (CAD/CAM) all-ceramic crowns made from digital and conventional impressions. MATERIALS AND METHODS: A dentoform tooth (#30) was prepared for an all-ceramic crown (master die). Thirty type IV definitive casts were made from 30 polyvinyl siloxane (PVS) impressions. Thirty resin models were produced from thirty Lava Chairside Oral Scanner impressions. Thirty crowns were pressed in lithium disilicate (IPS e.max Press; 15/impression technique). Thirty crowns were milled from lithium disilicate blocks (IPS e.max CAD; 15/impression technique) using the E4D scanner and milling engine. The master die and the intaglio of the crowns were digitized using a 3D laser coordinate measurement machine with accuracy of ±0.00898 mm. For each specimen a separate data set was created for the Qualify 2012 software. The digital master die and the digital intaglio of each crown were merged using best-fitting alignment. An area above the margin with 0.75 mm occlusal-gingival width circumferentially was defined. The 3D marginal fit of each specimen was an average of all 3D gap values on that area. For the 2D measurements, the marginal gap was measured at two standardized points (on the margin and at 0.75 mm above the margin), from standardized facial-lingual and mesial-distal digitized sections. One-way ANOVA with post hoc Tukey's honestly significant difference and two-way ANOVA tests were used, separately, for statistical analysis of the 3D and 2D marginal data (alpha = 0.05). RESULTS: One-way ANOVA revealed that both 3D and 2D mean marginal gap for group A: PVS impression/IPS e.max Press (0.048 mm ± 0.009 and 0.040 mm ± 0.009) were significantly smaller than those obtained from the other three groups (p < 0.0001), while no significant differences were found among groups B: PVS impression/IPS e.max CAD (0.088 mm ± 0.024 and 0.076 mm ± 0.023), C: digital impression/IPS e.max Press (0.089 mm ± 0.020 and 0.075 mm ± 0.015) and D: digital impression/IPS e.max CAD (0.084 mm ± 0.021 and 0.074 mm ± 0.026). The results of two-way ANOVA revealed a significant interaction between impression techniques and crown fabrication methods for both 3D and 2D measurements. CONCLUSIONS: The combination of PVS impression method and press fabrication technique produced the most accurate 3D and 2D marginal fits.

Low temperature sintering of fluorapatite glass-ceramics.

Fluorapatite glass-ceramics have been shown to be excellent candidates as scaffold materials for bone grafts, however, scaffold production by sintering is hindered by concurrent crystallization of the glass. Objective, our goal was to investigate the effect of Ca/Al ratio on the sintering behavior of Nb-doped fluorapatite-based glasses in the SiO2-Al2O3-P2O5-MgO-Na2O-K2O-CaO-CaF2 system. Methods, glass compositions with Ca/Al ratio of 1 (A), 2 (B), 4 (C) and 19 (D) were prepared by twice melting at 1525°C for 3h. Glasses were either cast as cylindrical ingots or ground into powders. Disk-shaped specimens were prepared by either sectioning from the ingots or powder-compacting in a mold, followed by heat treatment at temperatures ranging between 700 and 1050°C for 1h. The density was measured on both sintered specimens and heat treated discs as controls. The degree of sintering was determined from these measurements. Results and Significance XRD showed that fluorapatite crystallized in all glass-ceramics. A high degree of sintering was achieved at 775°C for glass-ceramic D (98.99±0.04%), and 900°C for glass-ceramic C (91.31±0.10). Glass-ceramics A or B were only partially sintered at 1000°C (63.6±0.8% and 74.1±1.5%, respectively). SEM revealed a unique microstructure of micron-sized spherulitic fluorapatite crystals in glass-ceramics C and D. Increasing the Ca/Al ratio promoted low temperature sintering of fluorapatite glass-ceramics, which are traditionally difficult to sinter.

How and when does fabrication damage adversely affect the clinical performance of ceramic restorations?

OBJECTIVES: As compared to factory-processed ceramic parts, one unique trait of all-ceramic dental restorations is that they are custom-fabricated, which implies a greater susceptibility to fabrication defects. A variety of processing techniques is now available for the custom fabrication of all-ceramic single and multi-unit restorations, these include sintering, heat-pressing, slip-casting, hard machining and soft machining, all in combination with a final staining or veneering step. All these fabrication techniques, from shaping to firing, are associated with the production of flaws of various shapes and sizes, in conjunction with thermal residual stresses, all of which are capable of inducing failure. METHODS: This review will examine the various types of fabrication damage inherent to each technique and attempt to establish a relationship between fabrication defects and clinical performance of all-ceramic dental restorations with particular attention to their longevity in vivo. RESULTS: Failure mechanisms in dental ceramics can be very complex and often involve the combination of physical factors, to which are added patient and clinician-related variables such as restoration design and in vivo conditions. SIGNIFICANCE: Tremendous progress has been made in understanding the failure mechanisms of all-ceramic dental restorations over the past thirty years. It remains that there is still a need for laboratory tests that usefully simulate clinical conditions.

Differentiation of human mesenchymal stem cells on niobium-doped fluorapatite glass-ceramics.

OBJECTIVE: Our goal was to characterize the response of human mesenchymal stem cells (hMSCs) to a niobium-doped fluorapatite-based glass-ceramic (FAp). METHODS: The glass was prepared by twice melting at 1525 °C for 3 h, and cast into cylindrical ingots later sectioned into discs and heat-treated to promote crystallization of fluorapatite submicrometer crystals. Tissue culture polystyrene (TCP) was used as control. The surface of the FAp discs was either left as-heat treated, ground or etched. Initial cell attachment was assessed at 3 h. Proliferation and alkaline phosphatase (ALP) expression data were collected at days 1, 4, and 8. Cell morphology was examined using SEM, at days 2 and 4. Mineralization was evaluated by Alizarin Red staining and SEM. RESULTS: Initial cell attachment on as heat-treated, etched, or ground surfaces was similar to that of the positive control group (p>0.05). The percentage of area covered by living cells increased significantly on as heat-treated, etched, or ground surfaces between days 1 and 8 (p<0.05). There was no significant difference among groups in cell coverage at day 8, compared to TCP control. SEM revealed well spread polygonal cells with numerous filopodia, either attached to the ceramic surface or connected to neighboring cells. ALP expression at day 8 was significantly higher in osteogenic media compared to growth media on both FAp and control. FAp discs stained positively with Alizarin Red and calcium-rich mineralized granules associated with fibrils were observed by SEM at day 35. SIGNIFICANCE: hMSCs displayed excellent attachment, proliferation, and differentiation on niobium-doped FAp glass-ceramic.

State of the art of zirconia for dental applications.

Zirconia has been recently introduced in prosthetic dentistry for the fabrication of crowns and fixed partial dentures, in combination with CAD/CAM techniques. This review encompasses the specific types of zirconia available in dentistry, together with their properties. The two main processing techniques, soft and hard machining, are assessed in the light of their possible clinical implications and consequences on the long-term performance of zirconia. An update on the status of clinical trials occurring worldwide is provided.

Stabilized zirconia as a structural ceramic: an overview.

This review introduces concepts and background from the ceramics engineering literature regarding metastable zirconia ceramics to establish a context for understanding current and emerging zirconia-based dental ceramics.