Ilkka Kangasniemi

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 materials 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.

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.

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.

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.

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.

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.

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°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.

Effect of Hydroxyapatite and Titania Nanostructures on Early In Vivo Bone Response

PURPOSEnHydroxyapatite (HA) or titania nanostructures were applied on smooth titanium implant cylinders. The aim was to investigate whether nano-HA may result in enhanced osseointegration compared to nano-titania structures.nnnMATERIALS AND METHODSnSurface topography evaluation included detailed characterization of nano-size structures present at the implant surface combined with surface roughness parameters at the micro- and nanometer level of resolution. Microstructures were removed from the surface to ensure that bone response observed was dependent only on the nanotopography and/or chemistry of the surface. Early in vivo histological analyses of the bone response (4 weeks) were investigated in a rabbit model.nnnRESULTSnIn the present study, nano-titania-coated implants showed an increased coverage area and feature density, forming a homogenous layer compared to nano-HA implants. Bone contact values of the nano-titania implants showed a tendency to have a higher percentage as compared to the nano-HA implants (p = .1).nnnCONCLUSIONnThus, no evidence of enhanced bone formation to nano-HA-modified implants was observed compared to nano-titania-modified implants. The presence of specific nanostructures dependent on the surface modification exhibiting different size and distribution did modulate in vivo bone response.

Bonding Strengths of Titania Sol-Gel Derived Coatings on Titanium

Bioactive ceramic coatings have had poor adhesion to substrate. In this study, the bond strength (tensile strength) of titania gel coating to titanium substrate was studied. In the experiments three different pretreatments were used, namely sodium hydroxide corroding, plasma cleaning and titanium nitride coating. Also the effects of heating temperature, heating in vacuum and titanium surface roughness were studied. The sol properties were altered with valeric acid addition. Samples were analysed by SEM-EDX, AES, AFM and tested by bond strength gauge. Those samples in which the titanium surface was precorroded one hour in sodium hydroxide, predeposited by titanium nitride or ground improved the bonding strengths of titania coatings to over 24 MPa. In these samples a fracture occurred at the glue-coating interface.

RELATION BETWEEN AGGREGATION AND HETEROGENEITY OF OBTAINED STRUCTURE IN SOL-GEL DERIVED CAO-P2O5-SIO2

Potentially bioactive sol-gel derived CaO-P2O5-SiO2 systems are studied and the influence of aggregation mechanism on the gel structure is discussed. A rheological measuring technique is used to monitor the aggregation process and the results are related to heterogeneity of the obtained gel structure. The results indicate that heterogeneity is produced in the sol-gel transition when calcium nitrate and phosphoric acid are used as precursors of CaO and P2O5. This destroys the correlation between bioactivity and the calcium and phosphorus content of the gel derived glasses.