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Biomedical subjects

Jukka Seppälä

Publications and source records attributed to Jukka Seppälä.

13 recordsLinked to original sources
PubMed2006

Effects of incorporated drugs on degradation of novel 2,2'-bis(2-oxazoline) linked poly(lactic acid) films.

Earlier studies have indicated that the degradation rate of poly(lactic acid) (PDLLA) can be modified by using 2,2'-bis(2-oxazoline) as a chain extender in polymer synthesis to form a lactic acid-based poly(ester-amide) (PEA). In the present study, the effect of an incorporated drug on the degradation rate of the PEA was evaluated. The model drugs, neutral guaifenesin, acidic sodium salicylate (pK(a) 3.0) and basic timolol (pK(a) 9.2), were incorporated into solvent cast PDLLA and PEA films. The drug content in the films was 2% (w/w). The degradation studies were carried out in PBS (pH 7.4, 37 degrees C); the resulting decrease in molecular weight of polymers was determined by size exclusion chromatography and the weight loss of films was measured. In addition, the drug release from the films in PBS (pH 7.4, 37 degrees C) was studied. The model drugs were released from the PDLLA and PEA films in a biphasic or triphasic manner. The final fast release phase of the drugs from both PDLLA and PEA films started when the molecular weight (M(n)) of the polymer had decreased close to 15,000 g/mol. The degradation rate of the PDLLA films was clearly enhanced by incorporated sodium salicylate or timolol. Whereas, the degradation rate of the PEA film was not enhanced by the incorporated drugs. The present results indicate that when compared to the PDLLA film, degradation rate of the PEA film in the presence of the drug is more predictable.

Drug Delivery Systems↗
PubMed2005

Recent changes in trophic state of the Baltic Sea along SW coast of Finland.

Drawing reliable conclusions on changes in the trophic state of various subareas of the Baltic Sea is problematic, in large part because the monitoring of productivity parameters exhibiting high natural variability is based on sparse sampling. This emphasizes the importance of long-term data sets. Here we present a 30-year chlorophyll alpha data set from the western Gulf of Finland. The trophic state of the study area showed an increasing trend in the 1970s and 1980s manifested mainly as strengthened vernal blooms. This trend did not continue in the 1990s, and the seasonal phytoplankton biomass maxima since then has begun to show some bias toward the late summer. The changes in seasonal maxima of phytoplankton blooms probably reflect i) decreased availability of N suppressing the magnitude of the vernal bloom, which increases the P reserves for the summer, and ii) enhanced internal P loading, which further increases the summer P reserves.

Animals↗
PubMed2004

Injectable bioactive glass/biodegradable polymer composite for bone and cartilage reconstruction: concept and experimental outcome with thermoplastic composites of poly(epsilon-caprolactone-co-D,L-lactide) and bioactive glass S53P4.

Injectable composites (Glepron) of particulate bioactive glass S53P4 (BAG) and Poly(epsilon-caprolactone-co-D,L-lactide) as thermoplastic carrier matrix were investigated as bone fillers in cancellous and cartilagineous subchondral bone defects in rabbits. Composites were injected as viscous liquid or mouldable paste. The glass granules of the composites resulted in good osteoconductivity and bone bonding that occurred initially at the interface between the glass and the host bone. The bone bioactivity index (BBI) indicating bone contacts between BAG and bone, as well as the bone coverage index (BCI) indicating bone ongrowth, correlated with the amount of glass in the composites. The indices were highest with 70 wt % of BAG, granule size 90-315 microm and did not improve by the addition of sucrose as in situ porosity creating agent in the composite or by using smaller (<45 microm) glass granules. The percentage of new bone ingrowth into the composite with 70 wt % of BAG was 6-8% at 23 weeks. At the articular surface cartilage regeneration with chondroblasts and mature chondrocytes was often evident. The composites were osteoconductive and easy to handle with short setting time. They were biocompatible with low foreign body cellular reaction. Results indicate a suitable working concept as a filler bone substitute for subchondral cancellous bone defects.

Animals↗
PubMed2003

Pancreatin enhanced erosion of and macromolecule release from 2,2-bis(2-oxazoline)-linked poly(epsilon-caprolactone).

The degradation and erosion of solvent cast films and injection molded bars prepared from poly(epsilon-caprolactone) (PCL) and 2,2'-bis(2-oxazoline) linked poly(epsilon-caprolactone) (PCL-O) were evaluated in simulated gastric fluid (SGF) (pH 1.2, pepsin present) and in simulated intestinal fluid (SIF) (pH 7.5, pancreatin present). After incubation of the polymer films (10 mg) and bars (70 mg) in the medium, the resulting decrease in molecular weight (degradation) was determined by size exclusion chromatography and the weight loss of the preparations was measured. In addition, the effect of pancreatin on FITC-dextran (MW 4400) release from PCL and PCL-O microparticles, prepared by w/o/w double emulsion technique, was studied. No degradation or weight loss was observed for either PCL or PCL-O films in SGF (12 h incubation, 37 degrees C). When compared to PBS pH 7.4, pancreatin hardly enhanced the weight loss of PCL films and bars. In contrast, pancreatin enhanced substantially erosion of PCL-O films and bars. Unlike PCL preparations, the PCL-O preparations showed surface erosion in SIF. Pancreatin increased considerably FITC-dextran release from both PCL and PCL-O microparticles. In conclusion, the present results demonstrate the enzyme sensitivity of the novel PCL-O polymer. In addition, the results show that pancreatin present in intestinal fluid may substantially affect drug release from PCL based preparations.

Macromolecular Substances↗
PubMed2003

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.

Animals↗
PubMed2002

Biocompatibility, encrustation and biodegradation of ofloxacine and silver nitrate coated poly-L-lactic acid stents in rabbit urethra.

The purpose of this study was to evaluate the biocompatibility, encrustation and biodegradation properties of silver nitrate and ofloxacine blended caprolactone-L-lactide copolymer coated self-reinforced poly-L-lactic acid (SR-PLLA) urospirals in situ in the male rabbit urethra. SR-PLLA urospirals coated with 10% by weight silver nitrate or 5% by weight ofloxacine blended copolymer or pure copolymer were inserted into the posterior urethra of 18 male rabbits. No prophylactic antibiotics were given. The animals were sacrificed 1 or 6 months after insertion. Urethral tissue reactions were histologically scored semiquantitavely and the appearence of the stents assessed using scanning electron microscopy. The biodegradation time of SR-PLLA stents was remarkably reduced by the caprolactone coating. Silver nitrate and ofloxacine blended copolymer coated urospirals caused less tissue reaction than urospirals with a pure copolymer coating. Silver nitrate coating effectively prevented biofilm formation and stent encrustation. Silver nitrate and ofloxacine blended copolymer coated SR-PLLA urospirals had good biocompatibility properties in rabbit urethra. In particular, coating with silver nitrate may provide possibilities of preventing bacterial adhesion to bioabsorbable stents.

Animals↗
PubMed2002

Degradation of and drug release from a novel 2,2-bis(2-oxazoline) linked poly(lactic acid) polymer.

The degradation rate of poly(lactic acid) (PLA) is typically modified by copolymerization of the glycolide with lactide. In the present study, the degradation rate of PDLLA was modified by a novel linking of PLA with 2,2'-bis(2-oxazoline). This modification resulted in formation of a more rapidly degrading poly(ester amide) (PEA) for controlled drug release. The hydrolytic degradation of PDLLA and PEA films was studied in PBS (pH 7.4, USP XXIV, 37 degrees C); the resulting decrease in molecular weight was determined by size exclusion chromatography and the weight loss of films was measured. Drug releases of guaifenesin (mw 198.2), timolol (mw 332.4), sodium salicylate (mw 160.1) and FITC-dextran (mw 4400) from PDLLA and PEA films and microspheres were examined in PBS (pH 7.4, 37 degrees C). The degradation rate of PEA was substantially greater than that of PDLLA. The release profiles of all small model drugs (mw <332.4) from PDLLA films were biphasic or triphasic, while the release profiles of small model drugs from PEA films varied extensively. Due to the faster weight loss of PEA, FITC-dextran (mw 4400) was released substantially more rapidly from PEA microspheres than from PDLLA microspheres. In conclusion, all model drugs, except guaifenesin, were released faster from PEA preparations than from PDLLA preparations.

Biocompatible Materials↗
PubMed2002

Lactic acid based PEU/HA and PEU/BCP composites: Dynamic mechanical characterization of hydrolysis.

Lactic acid based poly(ester-urethane) (PEU-BDI) and its composites with 20 and 40 vol.% bioceramic filler were characterized prior to their use as biocompatible and bioabsorbable artificial bone materials. Morphological, dynamic mechanical properties, and degradation of these either hydroxyapatite or biphasic calcium phosphate containing composites were determined. Addition of particulate bioactive filler increased the composite stiffness and the glass transition temperature, indicating strong interactions between the filler and matrix. Materials were sterilized by gamma-irradiation, which reduced the average molecular weights by 30-40%. However, dynamic mechanical properties were not significantly affected by irradiation. Specimens were immersed in 0.85 w/v saline at 37 degrees C for 5 weeks, and changes in molecular weights, mass, water absorption, and dynamic mechanical properties were recorded. All the composite materials showed promising dynamic mechanical performance over the 5 weeks of hydrolysis. Average molecular weights of PEU-BDI and its composites did not change substantially during the test period. PEU-BDI retained its modulus values relatively well, and although the moduli of the composite materials were much higher, especially at high filler content, they exhibited faster loss of mechanical integrity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

In vitro evaluation of poly(epsilon-caprolactone-co-DL-lactide)/ bioactive glass composites.

In vitro bioactivity of composites of poly(epsilon-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 microm and 90-315 microm) 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 degrees C. Formation of Ca-P deposition on the surface of the composites after dissolution in simulated body fluid at 37 degrees 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.

Biocompatible Materials↗
PubMed2002

Drug release profiles from and degradation of a novel biodegradable polymer, 2,2-bis(2-oxazoline) linked poly(epsilon -caprolactone).

In the present study, poly (epsilon -caprolactone) (PCL) was modified by introducing oxamide groups into PCL (PCL-O). The degradation (decrease in molecular weight) and erosion (weight loss) of PCL and PCL-O films were studied in PBS (pH 7.4, USP XXIV, 37 degrees C, 26 weeks incubation). The release rates of guaifenesin (M(w) 198.2), griseofulvin (M(w) 352.8), timolol (M(w) 332.4), sodium salicylate (M(w) 160.1) and FITC-dextran (M(w) 4400) from PCL and PCL-O preparations (solvent cast films, compression-molded plates, midi injection-molded rods and microparticles) were examined in PBS (pH 7.4, 37 degrees C). The degradation rate of PCL-O film was faster than that of PCL film while no erosion was observed for either film. When compared to the corresponding drug release from PCL films, the release rates of low molecular weight drugs (M(w)< or =352.8) from PCL-O films were comparable, their releases from both films following closely square-root-of-time kinetics. These results indicate that the oxamide groups had no substantial effect on the release of the low molecular weight drugs. The exception was sodium salicylate which was released faster from PCL-O film. However, FITC-dextran release was notably faster from PCL-O microparticles than from those made of PCL. FITC-dextran release was a combination of diffusion and polymer degradation and thus, the faster degradation of PCL-O enhanced the release of FITC-dextran. In conclusion, the effects of the oxamide groups on drug release profiles were dependent on the drug release mechanisms.

Biodegradation, Environmental↗
PubMed2002

Self-reinforcement and hydrolytic degradation of amorphous lactic acid based poly(ester-amide), and of its composite with sol-gel derived fibers.

The self-reinforcing and hydrolytic degradation of an amorphous poly(ester-amide) (PEA) based on lactic acid have been studied and compared with those of poly-L-lactide (PLLA). The studied PEA-rods were self-reinforced (SR) by solid-state die drawing resulting double shear strength. The hydrolytic degradation of PEA was studied during exposure to phosphate buffered saline at pH 7.4 and at 37 degrees C for 18 weeks. The degradation and mechanical properties of PEA were also followed in a self-reinforced composite structure consisting of PEA and sol-gel derived SiO(2)-fibers (SGF, 8 wt %). The hydrolytic degradation of the SR-PEA-rods with and without SG-fibers was significantly faster than that of SR-PLLA-rods. The weight average molecular weight (Mw) of PEA decreased by 90% from the initial Mw during the first 6 weeks in hydrolysis, when the Mw of the PLLA decreased by 10%.

Journal Article↗
PubMedDate not supplied

Biodegradation of lactic acid based polymers under controlled composting conditions and evaluation of the ecotoxicological impact.

The biodegradability of lactic acid based polymers was studied under controlled composting conditions (CEN prEN 14046), and the quality of the compost was evaluated. Poly(lactic acids), poly(ester-urethanes), and poly(ester-amide) were synthesized and the effects of different structure units were investigated. The ecotoxicological impact of compost samples was evaluated by biotests, i.e., by the Flash test, measuring the inhibition of light production of Vibrio fischeri, and by plant growth tests with cress, radish, and barley. All the polymers biodegraded to over 90% of the positive control in 6 months, which is the limit set by the CEN standard. Toxicity was detected in poly(ester-urethane) samples where chain linking of lactic acid oligomers had been carried out with 1,6-hexamethylene diisocyanate (HMDI). Both the Flash test and the plant growth tests indicated equal response to initial HMDI concentration in the polymer. All other polymers, including poly(ester-urethane) chain linked with 1,4-butane diisocyanate, showed no toxicological effect.

Biodegradation, Environmental↗