Mika Jokinen

In vitro Ca-P precipitation on biodegradable thermoplastic composite of poly(ε-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.

Surface properties of in vitro bioactive and non-bioactive sol-gel derived materials.

The acid-base properties of several in vitro bioactive (able to form bone mineral-like calcium phosphate on their surfaces) and non-bioactive sol-gel processed oxides are studied. The amount of Lewis acid sites was calculated from the pyridine adsorption using the Langmuir adsorption model. The Henry adsorption model was used in cases where no specific affinity between the adsorbent and the probe molecule was observed. The results were used to calculate the specific amounts of acidic and basic sites on SiO2- and TiO2-based materials. The zeta potential was measured for dip-coated TiO2 films, calcium- and phosphate-doped TiO2 films and for a non-bioactive Al2O3 film. Also, the calcium phosphate formation in simulated body fluid on in vitro bioactive TiO2 film was studied with zeta potential measurements. The results showed dependence on the negative surface charge and the important role of calcium adsorption in the beginning of the calcium phosphate formation. Surface topography of the films was investigated with atomic force microscopy, including a detailed analysis of the peak heights and distribution over cross sections. It was observed that in vitro bioactivity was strongly dependent on the nanoscale dimensions. Consequently, the in vitro calcium phosphate formation seems to be due to both the chemical interactions and the surface structure.

Effect of synthesis parameters of the sol-gel-processed spray-dried silica gel microparticles on the release rate of dexmedetomidine.

The objective of this study was to evaluate the possibilities to control the release rate of dexmedetomidine (DMED) from different spray-dried silica gel microparticle formulations. Microparticles were prepared by spray drying a silica sol polymer solution containing the drug. Drug release was investigated both in vitro and in vivo. The influence of sol-gel synthesis parameters, like pH and the water/alkoxide ratio (r) of the sol, on the release behaviour of the drug was studied. Silica gel microparticles had a smooth surface. Microparticles prepared from diluted sol, however, were more aggregated and clustered. The drug release conformed to zero order release from microparticles prepared near the isoelectric point of silica (pH 2.3 and pH 3) and to the square root of time kinetics from microparticles prepared at pH 1 and pH 5. The release also showed a dual-phasic profile with an initial burst and after that a slower release period. The dexmedetomidine release conformed to zero order kinetics from microparticles prepared at water/ alkoxide ratios between r = 6 and r = 35 (at pH 2.3). The release rate was the slowest from microparticles prepared with water/ alkoxide ratio 35. The bioavailability of dexmedetomidine in dogs showed that the release was sustained from silica gel microparticles as compared with a subcutaneously administered reference dose of 0.1 mg.

Drug release from biodegradable silica fibers

Abstract Sol–gel derived biodegradable SiO 2 gel fibers have been prepared and characterized by Raman spectroscopy, SEM, 29 Si MAS NMR and TG–MS, respectively. An active component, dexmedetomidine hydrochloride, was incorporated in situ into the fiber structure, by adding it to the sol used for fiber spinning. The subsequent release of the active component was studied in vitro and shown to be determined by differences in the fiber structure, for which clear but indirect evidence was obtained from the different characterization methods used.

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.

Calcium phosphate formation and ion dissolution rates in silica gel-PDLLA composites

Sol-gel derived silicas are potential biomaterials both for tissue regeneration and drug delivery applications. In this study, both SiO(2) and calcium and phosphate-containing SiO(2) (CaPSiO(2)) are combined with poly-(DL-lactide) to form a composite. The main properties studied are the ion release rates of biologically important ions (soluble SiO(2) and Ca(2+)) and the formation of bone mineral-like calcium phosphate (CaP) on the composite surface. These properties are studied by varying the quality, content and granule size of silica gel in the composite, and porosity of the polymer. The results indicate that release rates of SiO(2) and Ca(2+) depend mostly on the formed CaP layer, but in some extent also on the granule size of silicas and polymer porosity. The formation of the bone mineral-like CaP is suggested to be induced by a thin SiO(-) layer on the composite surface. However, due to absence of active SiO(2) or CaPSiO(2) granules on the outermost surface, the suitable nanoscale dimensions do not contribute the nucleation and growth and an extra source for calcium is needed instead. The result show also that all composites with varying amount of CaPSiO(2) (10-60 wt%) formed bone mineral-like CaP on their surfaces, which provides possibilities to optimise the mechanical properties of composites.

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.

Bioactive Glass (S53P4) and Mesoporous MCM-41-Type SiO2 Adjusting In Vitro Bioactivity of Porous PDLLA

SiO2-based bioceramics, MCM-41-type SiO 2 and the bioactive glass S53P4, in composites with poly(D,L)lactide were studied in the simulated body fluid. The parameters controlling ion dissolutions and calcium phosphate formation were studied a nd the data was used to create multicomposites with locally varying properties ( .g., CaP formation on the other side, uninhibited silica dissolution and possibility to drug release from the other side of com posite)

MANUFACTURE AND IN VITRO BIOACTIVITY OF SOL-GEL-DERIVED SILICA FIBRE AND P(L/D,L)LA COMPOSITE

ABSTRACT Silica fibres and nonwoven fibre assemblies were prepared from TEOS-derived silica sols using sol-gel method and dry spinning technique. The same sols can be used to prepare different fibre structures and to control the biodegradation. Due to the glassy nature with a low elasticity and a porous 2-5 nm structure, the observed fibres were alone difficult to process by using mechanical methods. In order to avoid that, the nonwoven fibre was further hot-pressed onto one side of the melt-processed poly(L/DL)lactide 70/30 (PLA70) membrane. The aim was to study the in vitro biodegradation (silica release) and bioactivity of the fibre composites. The in vitro bioactivity and dissolution of the fibres were studied in a simulated body fluid. To monitor the surface topography and roughness of the silica fibres, a scanning probe microscopy with a tapping mode atomic force microscopy (AFM) was used. It was shown that it is possible to prepare silica fibre composites, which are able to form calcium phosphate in vitro. The calcium phosphate formation ability could be further guided to one side of the composite membrane with the help of pure silica fibres.