Jaana Rich

In vitro evaluation of poly(ε-caprolactone-co-dl-lactide)/ bioactive glass composites

In vitro bioactivity of composites of poly(e-caprolactone-co-DL-lactide) P(CL/DL-LA) containing different amounts (40, 60 and 70 wt%) of bioactive glass, S53P4, was evaluated. Two ranges of granule size of bioactive glass (<45 μm and 90–315 μm) were blended with P(CL/DL-LA) copolymer in a batch mixer. The composites were characterised by dynamic mechanical thermal analysis. The molecular weight and the melting temperature of the copolymer matrix were adjusted to enable the application of the composite material by injection below 50°C. Formation of Ca-P deposition on the surface of the composites after dissolution in simulated body fluid at 37°C was recorded by scanning electron microscopy. Degradation of the composite material was measured by water absorption and changes in the average molecular weights as a function of the dissolution time. In vitro bioactivity was found to be dependent on the weight fraction and granule size range of the bioactive glass used. The presence of the bioactive filler also accelerated the degradation compared with the neat polymer sample.

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.

Bone response to degradable thermoplastic composite in rabbits.

The aim of this study was to evaluate biologic behavior of a composite of bioactive glass (BAG) (S53P4) and copolymer of poly(epsilon-caprolactone-co-DL-lactide) in experimental bone defects in rabbits. Twenty New Zealand white rabbits were used for the study. Bone defects (4 x 6mm) were prepared in the medial surfaces of the femoral condyles and the tibia. Cavities were filled with three different composites: composite with 60 wt% of small BAG granules (granule size <45 microm) and composites with 40 and 60 wt% of large BAG granules (granule size 90-315 microm). Copolymer without BAG was used as a reference material. Follow-up period was 8 and 16 weeks. In the femur at 8 weeks all the samples were partly surrounded by fibrous capsule. New bone formation was noticed in the areas where glass granules were in direct contact with the bone. At 16 weeks fibrous capsule was thinner in all samples. Bone ingrowth was found in the superficial layers of the composites with large glass granules. However, the percent of direct bone contact decreased between 8 and 16 weeks (p < 0.05). In the tibia at 8 weeks all the samples showed fibrous encapsulation. At 16 weeks fibrous capsules were thinner or occasionally disappeared. Bone ingrowth was noticed in the samples with large glass granules. Further, new bone formation was found in the medullary cavity. No signs of polymer degradation were seen at any time point. It can be concluded that the composite of BAG (S53P4) and copolymer of poly(epsilon-caprolactone-co-DL-lactide) is biocompatible with the bone tissue within the 16 weeks implantation period.

In vitro evaluation of biodegradable ε-caprolactone-co-D,L-lactide/silica xerogel composites containing toremifene citrate

Abstract Poly(e-caprolactone-co- d,l -lactide) polymers were blended with toremifene citrate or with toremifene citrate impregnated silica xerogel in order to develop a controlled release formulation. The copolymers were synthesized by bulk polymerization and characterized by nuclear magnetic resonance, size exclusion chromatography and differential scanning calorimetry analyses. The in vitro release of toremifene citrate, an antiestrogenic compound, and silica was carried out in simulated body fluid (pH 7.4) containing 0.5 wt% sodium dodecylsulphate at 34°C. The in vitro release studies indicate that the release flux of toremifene citrate increases with increasing weight fraction of caprolactone in the copolymer. Silica xerogel had a minor enhancing effect on the release rate of toremifene citrate. Copolymers containing larger amounts of d,l -lactide (PLA–CL20 and PLA–CL40 copolymers) were not suitable matrices for the delivery of toremifene citrate in a controlled manner because of the burst effect. The fraction of toremifene citrate released from PLA–CL80 matrix increased with the increasing loading of toremifene citrate. The results of the study indicate that the in vitro release of toremifene citrate can be adjusted by varying the polymer composition and also the initial drug loading.

Effect of the molecular weight of poly(ε-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.

Porous Biodegradable Scaffold: Predetermined Porosity by Dissolution of Poly(ester-anhydride) Fibers from Polyester Matrix

A novel selective leaching method for the porogenization of the biodegradable scaffolds was developed. Continuous, predetermined pore structure was prepared by dissolving fast eroding poly(epsilon-caprolactone)-based poly(ester-anhydride) fibers from the photo-crosslinked poly(epsilon-caprolactone) matrix. The porogen fibers dissolved in the phosphate buffer (pH 7.4, 37 degrees C) within a week, resulting in the porosity that replicated exactly the single fiber dimensions and the overall arrangement of the fibers. The amount of the porosity, estimated with micro-CT, corresponded with the initial amount of the fibers. The potential to include bioactive agents in the porogen fibers was demonstrated with the bioactive glass.

In Vivo Behavior of Poly(∈-Caprolactone-co-DL-Lactide)/Bioactive Glass Composites in Rat Subcutaneous Tissue

In this study, tissue reactions and possible toxicological responses of two different bioactive and degradable composite materials consisting of poly( ∈-caprolactone-co-DL-lactide) and bioactive glass (S53P4) granules were evaluated. The chosen materials were implanted subcutaneously in the back of rats for six months. The glass granules retained their bioactivity within the polymer matrices. A fibrous capsule formed around all tested materials and around the materials containing bioactive glass the fibrous capsules appeared to be thicker. Tissue growth into these materials was observed during the healing period while no growth was noticed into the plain polymer matrices. No adverse reactions were seen with any of the evaluated materials.

Bioactive glass induced in vitro apatite formation on composite GBR membranes

The aim of this study was to investigate inxa0vitro bioactivity of different thermoplastic biodegradable barrier membranes. Three experimental GBR membranes were fabricated using Poly(ε-caprolactone-co-d,l-lactide) P(CL/DL-LA) and particulate bioactive glass S53P4 (BAG; granule size 90–315xa0μm): (A) composite membrane with 60-wt.% of BAG, (B) membrane coated with BAG; and (C) copolymer membrane without BAG. Membranes were immersed in simulated body fluid (SBF), and their surfaces were characterized with SEM, XRD and EDS after 6 and 12xa0h and after 1, 3, 5, 7, and 14xa0days. Calcium phosphate (Ca-P) surface formation was observed on both composite membranes (A and B) but not on the copolymer membrane without bioactive glass (C). The Ca-P precipitation appeared to be initiated on the bioactive glass followed by growth of the layer along the polymer surface. In 6–12xa0h ion dissolution of the bioactive glass led to formation of the silica rich layer on the surface of the exposed glass granules on composite membrane B whereas only small amounts of silica was observed on the polymer surface of the composite membrane A. At 24xa0h nucleation of Ca-P precipitation was observed, and by 3–5xa0days membrane surface was covered with a uniform Ca-P layer transforming from amorphous to low crystalline structure. At 7xa0days composition and structure of the apatite surface resembled the apatite in bone. Once nucleated, the surface topography seemed to have significant effect on the growth of the apatite layer.