Isocyanato- and methacryloxysilanes promote Bis-GMA adhesion to titanium.

In dentistry, adhesion promotion with 3-methacryloyloxypropyltrimethoxysilane is usually sufficient, but its hydrolytic stability is a continuous concern. The hydrolytic stability of an alternative, 3-isocyanatopropyltriethoxysilane, was compared with that of conventional 3-methacryloyloxypropyltrimethoxysilane. Two silanes, both in 0.1 and 1.0 vol-% in ethanol-water, were evaluated in the attachment of an experimental bis-phenol-A-diglycidyldimethacrylate (Bis-GMA) resin to grit-blasted (with two different systems) titanium. Silane hydrolysis was monitored by FTIR spectrometry. Bis-GMA resin was applied and photo-polymerized on titanium. The specimens were thermocycled (6000 cycles, 5-55 degrees C). Surface analysis was carried out with scanning electron microscopy. Statistical analysis (ANOVA) showed that the highest shear bond was achieved with 0.1% 3-isocyanatopropyltriethoxysilane (12.5 MPa) with silica-coating, and the lowest with 1.0% 3-methacryloyloxypropyltrimethoxysilane (3.4 MPa) with alumina-coating. The silane, its concentration, and the grit-blasting method significantly affected the shear bond strength (p < 0.05). SEM images indicated cohesive failure of bonding, and, in conclusion, 3-isocyanatopropyltriethoxysilane is a potential coupling agent.

In vitro evaluation of sol-gel processed spray dried silica gel microspheres as carrier in controlled drug delivery.

The objective of this study was to evaluate sol-gel-derived spray dried silica gel microspheres as carrier material for dexmedetomidine HCl and toremifene citrate. The drug was dissolved in sol-gel processed silica sol before spray drying with Büchi laboratory scale equipment. Microspheres with a low specific surface area were spherical by shape with a smooth surface without pores on the external surface. The particle size distribution was quite narrow. The in vitro release of toremifene citrate and dexmedetomidine HCl showed a dose-dependent burst followed by a slower release phase, that was proportional to the drug concentration in the concentration range between 3.9 and 15.4 wt.%. The release period for toremifene citrate was approximately 10 days and for dexmedetomidine HCl between 7 and 50 days depending on drug concentration. Spray drying is a promising way to produce spherical silica gel particles with a narrow particle size range for controlled delivery of toremifene citrate and dexmedetomidine HCl.

Effect of aging time of sol on structure and in vitro calcium phosphate formation of sol-gel-derived titania films.

Titanium and its alloys have been used successfully in the manufacture of orthopedic and dental implants to replace damaged bone tissue. In this study, different sol-gel-derived TiO(2) coatings were produced on titanium substrates using different aging times (5, 10, 24, or 48 h) of the sol before dipping the coatings and varying numbers (one, three, or five) of coating layers. The influence of the aging time of the sol on the structure of the titania coatings with respect to in vitro bioactivity was investigated. The in vitro bioactivity tests were done in a simulated body fluid (SBF). The sol properties were monitored using a capillary viscometer and dynamic light scattering to determine the viscosity and particle size, respectively. The topography of the films was characterized using atomic force microscopy. The various sol aging times and numbers of layers produced differences in the topography of the titania films. For the coatings with one and three layers, the aging of the sols had an influence on the height of the peaks (lower with longer aging times) although the peak distance was about the same. The number of coating layers had a stronger influence. The distribution of the peak distances became narrower with an increasing number of coating layers. The coating with three layers (top coating prepared after 24 h of sol aging) and the coatings with five layers had a similar distribution of peak distances (15-50 nm), which was favorable for calcium phosphate formation. On these substrates, calcium phosphate formation started within 3-6 days of immersion in SBF. The aging time of the titania sol and the number of coating layers were found to have a strong influence on the surface topography in the nanometer scale of the titania films. The results indicate that the topography of the outermost surface is of importance for in vitro bioactivity.

Silica xerogel carrier material for controlled release of toremifene citrate.

Sol-gel processed silica xerogel was used as a carrier material for toremifene citrate in order to develop an implantable controlled release formulation which could be localised to a desired site providing targeted and long-lasting disease control and resulting in a reduced amount of drug needed. Toremifene citrate, an anti-estrogenic compound, was incorporated into silica xerogel matrixes during polycondensation of organic silicate, tetraethyl ortho silicate (TEOS). The effects of drug amount, drying temperature and polyethylene glycol (PEG) on the release rate of toremifene citrate and degradation of the silica xerogel matrixes were investigated. Addition of PEG (M(w) 4600/10000) decreased the specific surface area of the matrix and lowered the release rate of the drug. Reducing the amount of drug in the matrix also decreased the release rate of toremifene citrate. However, drying temperature did not affect the release rate of silica or toremifene citrate. The release profiles of toremifene citrate were according to zero order kinetics, suggesting that drug release was controlled by erosion of the silica xerogel matrix. These results suggest that the toremifene citrate release rate can be controlled to some extent by adding (PEG) or by varying the amount of drug in the silica xerogel matrix.

Silica xerogel as an implantable carrier for controlled drug delivery--evaluation of drug distribution and tissue effects after implantation.

The purpose of the present study was to examine controlled delivery of toremifene citrate from subcutaneously implanted silica xerogel carrier and to evaluate silica xerogel related tissue effects after implantation. Toremifene citrate was incorporated into hydrolyzed silica sol in a room temperature process. Toremifene citrate treated silica xerogel implants were tested both in vitro and in vivo using healthy mice. Silica xerogel with tritium-labelled toremifene was implanted subcutaneously in mice for 42 d. To determine the amount of tritiated toremifene remaining in the silica discs at the implantation site, the discs were excised periodically and radioactivity measured. The amount of tritiated toremifene in the implant after 42 d was still about 16% and the amount of silica xerogel about 25%. In a histopathological study silica xerogel did not show any tissue irritation at the site of the implantation. A fibrotic capsule was formed around the implant. No silica xerogel related histological changes in liver, kidney, lymph nodes and uterus were observed during the implantation period. The silica xerogel discs showed a sustained release of toremifene citrate over 42 d. Histologically, toremifene-related changes in the uterus were also detectable at all studied time points. These findings suggest that silica xerogel is a promising carrier material for implantable controlled drug delivery system.

In vitro release behavior of toremifene citrate from sol-gel processed sintered silica xerogels.

Factors affecting the adsorption and desorption of toremifene citrate (TC) on sintered silica xerogels were investigated in vitro. TC was attached onto sol-gel processed sintered silica xerogel grains or disks by adsorption. The adsorption of TC on the surface of silica was pH dependent. The results support the conclusion that large pore size results in highest drug adsorption. Adsorption of TC was most effective in xerogels sintered at 700 degrees C and containing the largest pores and lowest specific surface area of the silica xerogels studied in the adsorption tests. The release of TC from the xerogel matrix was linear with respect to the square root of time. The release of TC from the grains was very rapid for the first 5 hr, followed by a slower release. All drug was released from the grains, and 60% to 80% was released from the disks in 24 hr. All drug-silica xerogel formulations showed sustained in vitro release profiles.

Calcium phosphate formation on porous sol-gel-derived SiO2 and CaO-P2O5-SiO2 substrates in vitro.

Sol-gel-derived SiO2 and CaO-P2O5-SiO2 have been shown to be bioactive and bone bonding. In this study bioactive sol-gel-derived SiO2 and CaO-P2O5-SiO2 systems were tested for in in vitro bioactivity. The calcined ceramic monoliths were immersed in a simulated body fluid and analyzed to follow the hydroxyapatite formation on the ceramic surface. Apatite-forming ability was investigated in terms of structural changes by changing the composition and the preparation method. The role of Ca and P dopants in the substrate structure is complicated, and careful characterization is needed. The composition and structure together determine the in vitro bioactivity. The pore structure was analyzed using N2-adsorption/desorption isotherms. The results indicate that a great mesopore volume and a wide mesopore size distribution favor hydroxycarbonate apatite nucleation and a great surface area is not needed. The performed preparation process for silica in a basic environment provides a convenient way to prepare a mesoporous material.

Sol-gel-processed sintered silica xerogel as a carrier in controlled drug delivery.

Sol-gel-processed sintered silica xerogel was studied as a controllable, dissolvable, implantable material. The erosion of the matrix and the release of the preadsorbed drug toremifene citrate was investigated both in vitro and in vivo using mice. In an in vitro dissolution study, 50 to 60% of the drug was released after 24 h, according to the square root of time kinetics, and the weight loss of the silica was 24 wt %. Silica xerogel with tritium-labeled toremifene was implanted subcutaneously in mice for 56 days. To determine the amount of tritiated drug remaining in the silica disks at the implantation site, the disks were excised periodically and the radioactivity measured. About 40% of the radioactivity was released during the first 4 days and all of it within 28 days. Radioactivity also was measured in the liver, lungs, kidneys, uterus, and blood. The radioactivity reached a maximum level after 4 days in the liver, kidneys, and lungs and slowly decreased until all of the drug had been released from the matrix after 28 days. After release of the drug (28 days) the amount of remaining silica xerogel implant was 45 wt %, and at the end of the study (56 days) it was 24 wt %. In the histopathological study, sintered silica xerogel did not show any tissue toxicity at the site of the implantation, in the liver, or in the kidneys. It was concluded that sintered silica xerogel is a biocompatible and controllably resorbable material and therefore is a promising matrix for use in the sustained delivery of drugs.

Calcium phosphate induction by sol-gel-derived titania coatings on titanium substrates in vitro.

Titanium and its alloys are used widely in the manufacture of orthopedic and dental implants. Sol-gel-prepared titania is able to stimulate bone-like apatite formation in in vitro and in vivo cultures. These materials can be used, for example, as coatings on dental and orthopedic implants. However, the processes that lead to apatite formation are not fully understood. In this study different kinds of titania coatings on commercially pure titanium (c.p. Ti) were tested for apatite-forming ability. The rate of apatite formation is considered to be descriptive of a material's bioactive (bone-bonding) potential. Apatite-forming tests were done in simulated body fluid (SBF). Apatite-forming ability was highest with the addition of valeric acid to sol (600 degrees C) or with sintering sol-gel coatings at 450 degrees-550 degrees C. At that temperature range calcium phosphate forms on the coatings in 1 week. Calcium phosphate forming is observed in 1 day on standard coatings sintered at 500 degrees C.

Subchondral bone and cartilage repair with bioactive glasses, hydroxyapatite, and hydroxyapatite-glass composite.

The repair of an osteochondral defect in rabbit femur was studied with three kinds of bioactive glasses (BG), hydroxyapatite (HA), and hydroxyapatite-glass (HAG) composite. Seventy-two osteochondral defects were created in 18 rabbits. Sixty-four cylinders were implanted and eight defects were left empty as controls. Histomorphometry, scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDXA) were used for evaluation. Small osteochondral defects in rabbit femur found to heal themselves by regeneration. The three BGs, HA, and HAG led to direct lamellar bone repair of subchondral bone and restoration of articular surfaces mostly with hyalinelike cartilage in 12 weeks. However, the composition of the materials affects their behavior. Chondrogenesis took place earlier with the BGs than with HA. HAG degraded too much, glass 14 was too reactive and brittle, and the high alumina content in glass 11 disturbed its bone-bonding ability. Glass 7 and HA were the most balanced in the repair process. A special preparation method was used to retain soft tissues fairly unchanged and enable them to the observed together with hard tissues in SEM analysis.

Polymethylmethacrylate composites: disturbed bone formation at the surface of bioactive glass and hydroxyapatite.

The effects of polymethylmethacrylate on bone formation were studied alone and as composites in combination with hydroxyapatite and bioactive glass in the rabbit subchondral femur. Radiographs, histology, computer assisted histomorphometry, scanning electron microscopy and energy dispersive X-ray analysis were used for evaluation. A total of 60 cones were implanted for 3, 6 and 12 weeks. The composite cones consisted of granules of bioactive glass (S56.5P4) or hydroxyapatite embedded in polymethylmethacrylate. Pure polymethylmethacrylate cones served as controls. At the interface of the cones, bone contact was observed only when bioactive glass or hydroxyapatite was present at the cone surface. Fibrous tissue was always found at the polymethylmethacrylate-tissue interface. The osteoconductive bone formation at the surface of bioactive glass and hydroxyapatite was disturbed by polymethylmethacrylate. It seemed to resist bone formation at the interface of both bioactive glass and hydroxyapatite. However, bioactive glass was better able to withstand the detrimental effect of polymethylmethacrylate than hydroxyapatite.

In vivo calcium phosphate formation induced by sol-gel-prepared silica.

Implantation with plugs made of a porous sol-gel-prepared silica into the femurs of goats demonstrated that a calcium phosphate was formed both on the silica plugs and within the pores inside the silica plugs 12 weeks postoperatively. This observation indicates that a highly hydrated silica surface is effectively catalytic for calcium phosphate nucleation. Calcification can be triggered in physiologic solution under stimulation of the silica gel. A high level of silicon in the uncalcified osteoid region of young bone is thus thought to provide a number of SiOH groups for initiating calcium phosphate formation. Our results provide some information about the mechanism of calcium phosphate mineralization in higher animals. We believe that heterogeneous nucleation of apatite can be induced from metastable calcium phosphate solutions including physiologic fluids on those specific surfaces of materials, where there are abundant acidic OH groups.

In vivo reactions of Ca,P particle containing surface reactive glasses.

Four Ca,P particle containing surface reactive glass composites and two glasses (in the SiO2-CaO-P2O5-Na2O-Al2O3-B2O3 system) were implanted in the diaphyseal area of goat femora up to 24 weeks. Scanning electron microscopic, energy dispersive x-ray, and histological analysis were performed to evaluate the material-tissue interactions. A new type of integration mechanism was observed. Instead of the bone growing to the material surface, a gel-like silica formation appeared between the cortex bone and the material surface. In time the gel-like formation was replaced by a Ca,P layer. The results provided indirect evidence that pure silica gel formed in the tissues could also achieve an apatite layer formation and bone bonding on its surface.

In vivo tensile testing of fluorapatite and hydroxylapatite plasma-sprayed coatings.

A tensile test has been developed to test bioactive coating materials. Hydroxylapatite (HA) and fluorapatite (FA) coatings with various roughnesses were tested using sandblasted titanium (Ti) as a control material. Twelve goats received 7 implants each for 6 (2 goats), 12 (5), and 24 (4) week implantation periods. After 12 weeks the mean tensile strength values were highest for polished hydroxylapatite (HAP) followed by HA > FAP (polished fluorapatite) > FA > Ti, and hydroxylapatite type coatings were found to exhibit significantly higher values than fluorapatite type coatings or titanium implants. After 24 weeks no statistically significant differences could be found between any of the implant types. The order of the mean strength values was now HAP > HA > FA > FAP > Ti. Fracture always occurred between the coating and titanium if bone contact had been established. In conclusion, it is suggested that results from different types of test methods cannot be used to compare different types of bioactive coatings.

Dissolution and scanning electron microscopic studies of Ca,P particle-containing bioactive glasses.

Calcium phosphate (Ca,P) precipitation behavior on the surface of two bioactive glasses and four bioactive glass composites--two with hydroxylapatite (Ca10(PO4)6 (OH)2) and two with rhenanite (CaNaPO4)--were studied in simulated body fluid (SBF) and in Tris-Buffer at 5, 8, 16, 24, 48, 72, and 144 h. The weight loss of the materials was measured and the amount of precipitation was estimated using scanning electron microscopy with electrochemical detection (SEM-EDX) analysis. The test was repeated for one glass and its respective rhenanite composite every 3 h until 60 h and thereafter every 10 h until 150 h in SBF. Atomic absorption spectroscopy, spectrophotometry, SEM-EDX analysis, and pH measurements were performed on these samples. It is shown that in vitro the composite materials have a higher capacity for Ca,P precipitation than the glasses. Weight losses of the materials correlate well with their composition. Both the glass and Ca,P phases influence the precipitation mechanism and rate. Precipitation begins preferably from the glass phase. Ca,P particles clearly influence the time of onset and rate of precipitation. Cross-sectional EDX analysis of the samples revealed an absence of a clear Si-rich layer in glass A0B0 (SiO2 53.9 mol %, Na2O 27.5, CaO 12.4, P2O5 6.2, Al2O3 0.0 and B2O3 0.0) composites. This was attributed to the presence of extra calcium and phosphate ions on the surface of the material. The ion-concentration and pH change curves offered insight into the mechanism of precipitation. A connection was established between SEM-EDX results and the release curves. Formation of an Si,Ca,Na film was observed that seemed to initiate the Ca,P precipitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Preparation of dense hydroxylapatite or rhenanite containing bioactive glass composites.

The effect of time at 600 degrees C and of small additions of Al2O3 and B2O3 on the sintering of two composite materials of (1) hydroxylapatite (Ca10(PO4)6(OH)2) and bioactive glass (SiO2-CaO-P2O5-Na2O) or (2) rhenanite (CaNaPO4) and bioactive glass were studied. Scanning microscopy, quantitative EDX, x-ray diffraction, helium gas density measurements, and diametral measurements were performed on the resulting composites. No reactions were observed with the SEM or XRD between the hydroxylapatite particles and the glass matrix within sufficient sintering times to achieve maximum density. The rheunanite-containing composites were observed to form Na2O2CaO3SiO2 crystals by x-ray diffraction, probably as a result of dissolution of the rhenanite particle surfaces into the glass phase, the crystals formed in the glass or at the interface of the glass, and the ceramic particles. However, within the short sintering times needed to achieve maximum density the rhenanite particles remained mostly intact. The rhenanite-containing materials gave better results than the hydroxylapatite-containing materials. The glass composition had a great effect on the densification process.

Calcium phosphate formation at the surface of bioactive glass in vitro.

The calcium phosphate formation at the surface of bioactive glass was studied in vitro. Glass rods and grains were immersed in different aqueous solutions and studied by means of scanning electron microscopy and energy dispersive x-ray analysis. Surface morphological changes and weight loss of corroded grains were monitored. In-depth compositional profiles were determined for rods immersed in the different solutions. The solutions used were tris-buffer (tris-hydroxymethylaminomethane + HCl), tris-buffer prepared using citric acid (tris-hydroxymethylaminomethane + C6H8O7.H2O), and a simulated body fluid, SBF, containing inorganic ions close in concentration to those in human blood plasma. It was found that the calcium phosphate formation at the surface of bioactive glass in vitro proceeds in two stages. When immersing the glass in tris or in SBF a Ca,P-rich surface layer forms. This accumulation takes place within the silica structure. Later, apatite crystals forming spherulites appear on the surface. The Ca/P-ratio of initially formed calcium phosphate was found to be about unity. It is proposed that this is due to bonding of phosphate to a silica gel. The surface is stabilized, i.e., leaching is retarded, by the rapid Ca,P-accumulation within the silica structure before apatite crystals are observed on the surface. It is proposed that the initially formed calcium phosphate is initiated within the silica gel. The crystallizing surface provides nucleation sites for extensive apatite formation on the glass surface. In the presence of citrate no Ca,P-accumulation occur at the glass surface, but soluble Ca-citrate complexes form. By comparing the weight loss during corrosion in tris with that in the calcium and phosphate containing SBF, it is possible to establish whether the glass can induce apatite formation at its surface or not.