Biomimetic mineralization of partially bioresorbable glass fiber reinforced composite.

The aim of this study was to investigate the biomimetic mineralization on the surface of a glass fiber reinforced composite with partially resorbable biopolymer matrix. The E-glass fibers were preimpregnated with a novel biopolymer of poly(hydroxyproline) amide, and further impregnated in the monomer system of bis-phenyl glycidyl dimethacrylate (Bis-GMA)--triethylene glycol dimethacrylate (TEGDMA), which formed interpenetrating polymer networks (IPN) with the preimpregnation polymer. After light-initiated polymerization of the monomer system, the rhombic test specimens (n = 6) were immersed in the simulated body fluid (SBF) with the bioactive glass for 24 h, and then the apatite nuclei were allowed to grow for 1, 3, 5 and 7 days in the SBF. The control test specimens (n = 3) were immersed in SBF without the bioactive glass. According to the scanning electron microscope (SEM), a mineral layer was formed on the surface of all the specimens, which were immersed with bioactive glass. The layer was thickened by the prolonged immersion time to a uniform layer. The Ca/P atomic ratio of the mineral varied between 1.30 and 1.54 as analyzed by the energy dispersive X-ray analysis (EDXA). The Fourier transform infrared spectroscopy (FT-IR) spectra gave signals for the mineral, which are characteristic of both bone-like apatite and orthocalciumphosphate. In conclusion, the mineral layer was formed on the surfaces of the specimens by biomimetic mineralization, the mineral being a mixture of bone-like apatite, orthocalciumphosphate and other calcium phosphates.

Characterisation of bioactive glass coatings on titanium substrates produced using a CO2 laser.

Titanium and its alloys are widely used in load-bearing bioinert implants. Bioactive glasses (BAGs) form a chemical bond with bone, but they are not suitable for load-bearing applications. Creating a BAG coating on a titanium implant could combine the best properties of both materials. The results tend to be poor when conventional firing methods are applied to coat titanium with BAG. A local application of heat to melt the glass can be achieved by a CO2 laser. A new method is introduced to create BAG coatings on titanium locally in a controlled manner, with a focused CO2 laser beam. The coatings produced by this method precipitate calcium phosphate in vitro. Processing parameters (number of coated layers, laser power, and processing atmosphere) providing a firm attachment of the glass and good in vitro bioactivity were identified. XRD analysis showed no crystallisation of the glass due to processing with the laser. EDXA indicated the formation of a calcium phosphate layer, which FTIR suggested to be a hydroxyapatite. The results show CO2 laser processing to be a promising technique for the manufacture of 30-40 microm BAG coatings on titanium.

Flexural properties of glass fiber reinforced composite with multiphase biopolymer matrix.

The aim of this study was to evaluate flexural properties of glass fiber-reinforced composites with a multiphase biopolymer matrix. Continuous unidirectional E-glass fibers were preimpregnated with a novel biopolymer of poly(hydroxyproline) amide and ester. The preimpregnated fibers were then further impregnated in a co-monomer system of Bis-GMA-TEGDMA, which formed semi-interpenetrating polymer networks (semi-IPN) with the preimpregnated polymer. After light initiated polymerization of the monomer system, rectangular shaped bar specimens (n = 4) were tested by the three-point bending test. The control material was a fiber-reinforced composite with a Bis-GMA-TEDGMA-matrix only. The mean flexural strength of poly(hydroxyproline) amide preimpregnated fiber composite was higher than that of the control (FS = 888 vs. 805 MPa). The poly(hydroxyproline) ester preimpregnated fibers resulted in lower strength (FS = 541 MPa). The results of this study suggest that preimpregnation of glass fibers with poly(hydroxyproline) amide and the use of such fibers in fiber-reinforced composites with IPN polymer matrices, can reach relatively high mechanical properties.

In vitro cytotoxicity of E-glass fiber weave preimpregnated with novel biopolymer.

The aim of this study was to investigate cytotoxicity of composition of E-glass fibers and novel biopolymer of poly(hydroxyproline). Growth and proliferation of the human gingival fibroblast cells on the surface of the materials was evaluated. The number of cells grown and proliferated on cell culture plastic was used as a control. Bi-directional fiber weaves were preimpregnated with poly(hydroxyproline). Cytotoxicities of the preimpregnated and nonimpregnated materials were evaluated bythe release of lactate dehydrogenase from the cells during the culture period of 24 h. The values of the lactate dehydrogenase activity of the materials' extracts showed non-toxicity for poly(hydroxyproline) preimpregnated E-glass fiber weaves. The growth of fibroblasts on the surface of the materials appeared normal after 11 days culture period; they looked healthy and normal in size and shape. The results of this study suggest that based on its' non-cytotoxicity the composition of E-glass fibers and poly(hydroxyproline) can further be evaluated as a material that is suitable for biomedical use.

In vitro Ca-P precipitation on biodegradable thermoplastic composite of poly(epsilon-caprolactone-co-DL-lactide) and bioactive glass (S53P4).

Bioactive properties of composites containing poly(epsilon-caprolactone-co-DL-lactide) with molar ratio 96/4 and bioactive glass (BAG), S53P4, were tested in vitro. The glass content in the tested materials was 40, 60 or 70 wt%, and two granule size ranges (<45 and 90-315 microm) were used. The composites were analysed for their apatite-forming ability. This was determined as a function of time by the dissolution pattern of Si and Ca ions and structural changes on the specimen surfaces. Composite specimens were immersed in simulated body fluid at 37 degrees C for up to 6 months. The changes in Si and Ca concentrations of the immersion medium were determined with UV-Vis and atomic absorption spectrophotometry. The calcium phosphate precipitation and apatite formation were evaluated by scanning electron microscopy (SEM) and infra-red spectroscopy (IR) using the attenuated total reflectance (ATR) system. The SEM and SEM-EDX analysis of the depositions formed on the composite surfaces was in line with the changes in ion concentrations. The clearest results with IR were seen in the material containing 60 wt% small glass particles. The results indicate that composites containing over 40 wt% BAG granules are bioactive, and that a higher BAG surface area/volume ratio favors the apatite formation in vitro.

Local induction of calcium phosphate formation on TiO2 coatings on titanium via surface treatment with a CO2 laser.

Sol-gel-derived TiO(2) coatings are known to promote bonelike hydroxyapatite formation on their surfaces in vitro and in vivo. Hydroxyapatite integrates into bone tissue. In some clinical applications, the surface of an implant is simultaneously interfaced with soft and hard tissues, so it should match the properties of both. A new method is introduced for treating the coatings locally in a controlled manner. The local densification of sol-gel-derived titania coatings on titanium substrates with a CO(2) laser was studied in terms of the in vitro calcium phosphate-inducting properties. CO(2)-laser-treated multilayer coatings were compared with furnace-fired coatings prepared with the same recipe and previously shown to be bioactive. Additionally, local areas of furnace-fired multilayer coatings (previously shown to be bioactive in vitro) were further laser-treated to achieve various properties in the same implant. Topological surface properties were examined with atomic force microscopy. The formation of hydroxyapatite was studied with Fourier transform infrared and scanning electron microscopy energy-dispersive X-ray analysis. The results show that calcium phosphate formation can be adjusted locally by laser treatment. Calcium phosphate is a bonelike hydroxyapatite. The local treatment of sol-gel-derived coatings with a CO(2) laser is a promising technique for creating implants with various properties to interface different tissues and a possible way of coating implants that do not tolerate furnace firing.

Alkyl-substituted silica gel as a carrier in the controlled release of dexmedetomidine.

The effect of alkyl substitution of the silica xerogel matrix on the release rate of dexmedetomidine was evaluated. Silica sol was processed by either casting or spray drying. When the reaction precursor tetraethylorthosilicate (TEOS) was partially substituted with tri- or dialkoxysilane, the release of dexmedetomidine and degradation of the matrix were decreased compared with 100% TEOS-based gel. Increasing the number or length of the organic groups attached to silicon, modified the silica gel structure and reduced the release rate of dexmedetomidine from monoliths. The release of dexmedetomidine from alkyl-substituted silica gel microparticles, however, showed a burst in drug release. Subcutaneously administered silica xerogel matrices (manufactured by casting, containing 25 mol% dimethyldiethoxysilane at two different doses of dexmedetomidine) were studied in dogs. Sustained delivery of dexmedetomidine was obtained for at least 48 h.

Clinical survey of acrylic resin removable denture repairs with glass-fiber reinforcement.

PURPOSE: The aim of this study was to evaluate clinical usefulness and durability of continuous glass-fiber reinforcement in repair of acrylic resin removable dentures. MATERIALS AND METHODS: Fractured removable dentures without reinforcement, with conventional metal-wire reinforcement, or with mesh reinforcement were collected from two dental schools in Finland. The total number of dentures was 51 and the number of patients was 48. During the repair, the dentures were reinforced with a polymer-preimpregnated E-glass fiber at the region of the fracture. The fibers were used as partial fiber reinforcement, i.e., only the weakest part of the denture was reinforced. Follow-up time varied from 4 months to 4.1 years. After the follow-up period, possible fractures and discoloring were visually inspected. Possible irritation of oral mucosa by glass fibers and the general shape of the denture were also evaluated. RESULTS: In 88% of the cases, there was no need for adjustment at the region of partial fiber reinforcement, and the clinical condition of the dentures was good. Glass fibers did not irritate the oral mucosa. In the case of refracture or hairline fracture, positioning of the partial fiber reinforcement was incorrect or the reinforcement had been used incorrectly (the wetting of the reinforcement with denture base resin was inadequate). CONCLUSION: Polymer-preimpregnated partial fiber reinforcement seems to be useful in eliminating fractures of acrylic resin removable dentures. However, this study emphasizes the importance of correct positioning and accurate laboratory technique when partial fiber reinforcement is used.

In vitro release of heparin from silica xerogels.

Heparin, a powerful anticoagulant used for the prophylaxis of both surgical and medical thrombosis, was incorporated into a silica xerogel matrix during polycondensation of organic silicate. The influence of various chemical sol-gel parameters (the properties of reaction precursors, catalyst and final moisture content of the gel and heparin concentration) was studied. The release of heparin from the gel was according to zero order during the dissolution period and the release rate of heparin was proportional to the drug load in the concentration range between 6.8 and 13.6 wt%. It was found that the catalyst used for the preparation of the gel, the final moisture content and the chemical modification of silica xerogel network have an influence on the release rate of heparin. The released heparin from all the different xerogels studied retained about 90% of its biological activity.

In vitro bioactivity and structural features of mildly heat-treated sol-gel-derived silica fibers.

The ability of sol-gel-derived silica fibers heat treated at a low temperature to induce formation of bone-like calcium phosphate (HCA) on their surfaces provides alternatives for the design of novel biomaterials, for example as implants used in tissue guiding or bone repairs. In this study, dry spinning was used to prepare the sol-gel fibers, which were heat-treated at 175 degrees and 250 degrees C. In addition, the differences in the surface topography (in a nanometer scale) of different fibers with respect to their in vitro bioactivity were studied. The structure of the fibers was varied using three different factors: (1) spinnable sols having varying structures and sizes of silica polymers to establish varying viscosity levels; (2) aging of green-state fibers; and (3) heat treatment of fibers. The in vitro bioactivity and solubility tests were done in simulated body fluid (SBF). To monitor surface topography and roughness of the heat-treated silica fibers, a scanning probe microscopy (SPM) with tapping mode AFM was used. Different fibers obtained clearly different properties. The fibers spun at about eta > 3.0 Pas had the best properties with respect to bioactivity, especially when they were heat-treated at 175 degrees C. It was found that surface structure in a nanometer scale was the most important factor controlling the in vitro bioactivity of heat-treated silica fibers. The correct proportions between the peaks and peak distances at the surfaces are suggested to be important with respect to in vitro bioactivity. The results indicate that peak distance distribution between 5-50 nm, especially between 5-20 nm, together with a peak height > or = 1 nm is most favorable for calcium phosphate formation.

In vitro release of dexmedetomidine from silica xerogel monoliths: effect of sol-gel synthesis parameters.

Dexmedetomidine, an alpha 2-agonist, was incorporated as a hydrochloride salt into silica xerogel in order to evaluate the effect of sol-gel synthesis parameters: pH of the sol, water/alkoxide molar ratio, drug concentration and size of the device on the drug release rate and degradation rate of the matrix. This study showed that diffusion controlled the release of dexmedetomidine from silica xerogel prepared between pH 1 and pH 5. The drug release was, however, slowest near the zero charge of silica xerogel (pH 2-3). The burst of dexmedetomidine, a lipophilic, but in the form of hydrochloride salt water-soluble drug, was increased from the matrix prepared either below or above the isoelectric point. It follows that the optimum pH for preparing a drug delivery device for dexmedetomidine, is near the zero charge of silica xerogel, where the degradation of the matrix was also slowest. In addition to processing pH, the release rate of drugs can be controlled by changing the water/alkoxide molar ratio of the sol.

In vivo model for frontal sinus and calvarial bone defect obliteration with bioactive glass S53P4 and hydroxyapatite.

An in vivo model was developed to investigate the usability of a frontal sinus and a calvarial bone defect obliteration with bioactive glass S53P4 (BG) and hydroxyapatite (HA) granules. Roofs of 21 Elco rabbit frontal sinuses were drilled open from 4 separate holes using a standard method, and the sinuses, located in pairs, in frontal bone were filled with BG on one side and with HA on the other side. Two parallel posterior defects were covered with a pedicled periosteum flap, and 2 anterior defects with a free flap. The stability of materials, new bone, and connective tissue formation were observed with histomorphometry, scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDXA), and X-ray pictures at 1, 3, 6, and 12 months postoperatively. The results showed more rapid resorption of filling material (p = 0.019) and new bone formation (p = 0.0001) in the defects filled with BG than in the corresponding HA-filled defects studied by histomorphometry throughout the study. New bone formation and resorption of materials were faster in defects covered by a pedicled flap than by a free periosteum flap. The results were supported by SEM histomorphometric and radiologic analysis. Both bioactive materials studied were well tolerated in frontal sinuses and in calvarial bone defects. The experimental model showed the influence of early periosteum vascularization on accurate frontal sinus filling and the healing process in rabbit frontal sinuses.

Influence of sol and stage of spinnability on in vitro bioactivity and dissolution of sol-gel-derived SiO2 fibers.

The ability of the sol-gel-derived green state silica fibers to induce the formation of bone-like calcium phosphate (HCA) on their surfaces has not been studied earlier. Bioactive silica fibers provide alternatives for the design of novel products, e.g., as implants used in tissue guiding or bone repairs. In this study, dry spinning was used to prepare the sol-gel fibers. Different fibers with different bulk structures were prepared by changing the composition and controlling the stage of spinnability. Additionally, the influence of the aging time of the fibers on the bulk structure of the samples was investigated. Furthermore, the ability to form calcium phosphate was investigated in vitro in the simulated body fluid (SBF). Transmission electron microscopy was used to illustrate the bulk structure of the green state fibers and scanning electron microscopy to illustrate the formed calcium phosphate layer on the fibers. The fibers were additionally characterized by measuring the dissolution of the silica in the SBF. In vitro bioactive silica fibers were successfully prepared. The calcium phosphate layer was formed within 1-5 days in the best case. The structural stability and the in vitro bioactivity varied with the aging time expect in one case where practically stable fibers could be prepared. The concentration of silica released in the SBF had no direct connection with the HCA formation. The silica-rich gel layer was not observed on the fibers, but the structure of the fibers was suggested to have an important role in the HCA formation.

Effect of the molecular weight of poly(epsilon-caprolactone-co-DL-lactide) on toremifene citrate release from copolymer/silica xerogel composites.

The purpose of this study was to develop a biodegradable polymeric carrier system for toremifene citrate based on epsilon-caprolactone/DL-lactide copolymers and silica xerogel. The effect of the molecular weight of poly(epsilon-caprolactone-co-DL-lactide) affecting the release rate of toremifene citrate from copolymer/silica xerogel composites was evaluated by in vitro dissolution study. Lower and higher molecular weight copolymers (LMW 60000 g/mol and HMW 300000 g/mol) were used in the devices. Drug release was compared from the (copolymer/drug) matrix device and the (copolymer/drug impregnated silica xerogel) composite device. Hydrolysis of the copolymer devices was evaluated by water absorption, weight loss and change of molecular weight by size exclusion measurements (SEC). Controlled release of toremifene citrate was obtained from both matrix and composite devices and the release rate was most affected by the initial molecular weight of the copolymer. Throughout the study better results were obtained with LMW devices, since drug release was steady for nearly 1 year and no changes in the release rate were observed. The drug release was diffusion controlled from both LMW matrix and composite devices. Incorporation of toremifene citrate into the silica xerogel was found to enhance the drug release rate. The copolymer matrices degraded by random hydrolytic chain scission and, unexpectedly, HMW P(CL/LA) degraded faster than LMW P(CL/LA). The release of toremifene citrate from HMW devices was not complete before the second stage of polymer degradation began.

Clinical follow-up method for frontal sinus obliteration with bioactive glass S53P4.

A clinical follow-up method was developed to investigate the behavior of a massive amount of bioactive glass S53P4 (BG) clinically used in frontal sinus obliteration. Two sizes of granules (0.63-0.8 mm or 0.8-1.0 mm) in 16 separate BG amounts, weight 25 g, were tested both in simulated body fluid (SBF) and in a buffer containing tris-hydroxymethyl aminomethane citric acid (TRIS-c.a) in standard conditions. The dissolution of silicon (Si) and phosphate (P) was detected with direct current plasma atom emission spectroscopy (DCP-AES) monthly up to 6 months. The BG masses were scanned both wet in the solutions and dried by computer tomography (CT), and the scans were analyzed by Region of Interest (ROI) technique. Calcium phosphate (CaP)- and silica (Si)-gel-layers were studied by scanning electron microscopy (SEM) at 1, 3, and 6 months. Cumulative loss of Si and P was stronger in TRIS-c.a than in SBF (p < 0.0001), and it was higher with smaller than with larger granules in both solutions (p < 0.0001). This was shown correspondingly by the decrease of Hounsfield units (HUs) in ROI analysis (p < 0.0001). The level of HUs was lower with dried than with wet BG (p < 0.0001). The results were compared for clinical ROI analysis of patients with obliterated frontal sinuses up to 48 months and they were parallel. The follow-up method seems to indirectly reveal the behavior of BG and the healing process in the obliterated cavity.

Experimental follow-up model for clinical frontal sinus obliteration with bioactive glass (S53P4).

Bioactive glass S53P4 (BG) is an osteoconductive allograft material. Since 1990, BG has been used in the obliteration of frontal sinuses in more than 30 consecutive patients. The patients have been monitored regularly with clinical examinations, computer tomography (CT) scans, laboratory tests and, in a few cases, biopsies have also been obtained. The material has been well tolerated and no loss of volume of obliteration material has been seen in the obliterated sinuses. However, in repeated CT monitoring and with Region of Interest (ROI) analysis, a decrease in the density of the obliteration material inside the frontal sinuses has been seen. In the present study, the clinical conditions after an obliteration operation were simulated and the behaviour of the BG in the obliterated area was observed. The aim was to study whether it is possible indirectly to estimate the resorption of a massive amount of BG with ROI analysis for monitoring the clinical success of the treatment. Thus two sizes of granules (0.63-0.8 mm and 0.8-1.0 mm) in eight separate BG amounts, weight 25 g, were tested in simulated body fluid (SBF) in standard conditions. The dissolution of silicon (Si) and phosphate (P) was detected with direct plasma atom emission spectroscopy (DCP-AES) monthly up to 6 months. The BG amounts were scanned with CT and the slices analysed using the ROI technique at 1, 3 and 6 months. The cumulative loss of Si and P in SBF was significant during the study (p < 0.0001) and it was stronger with smaller than with larger granules (p < 0.0001). This was shown correspondingly by the decrease of Hounsfield units (p < 0.0001) in ROI analysis. The method seems reliably to reveal the resorption of BG for clinical purposes.

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.

In vitro model for frontal sinus obliteration with bioactive glass S53P4.

An in vitro model was used to investigate the behavior of a massive frontal sinus obliteration with bioactive glass S53P4 (BG) for clinical purposes. Two sizes of granules (0.63-0.8 mm or 0.8-1.0 mm) in 16 separate BG amounts, weight 25 g, were tested both in simulated body fluid (SBF) and a buffer containing trishydroxymethyl aminomethane citric acid (TRIS-c.a) in standard conditions. The dissolution of silicon (Si) and phosphate (P) was detected with direct current plasma atom emission spectroscopy (DCP-AES) monthly up to 6 months. The BG masses were scanned by computer tomography (CT) and the scans analyzed by Region of Interest (ROI) technique. Calcium phosphate (CaP)- and silica (Si)-gel-layers were studied by scanning electron microscopy (SEM) at 1, 3, and 6 months. Cumulative loss of Si and P was stronger in TRIS -c.a than in SBF (p < 0.0001), and it was higher with smaller than with larger granules in both solutions (p < 0.0001). This was shown correspondingly by the decrease in Hounsfield units (HU) by ROI analysis (p < 0.0001). In SBF-soaked BG masses, the CaP-layer occurred on the uppermost granules, and in TRIS-c.a at 3-6 months, on the granules in the center and lower parts. The decrease of HU seems to reveal indirectly the resorption of BG.

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.