Piotr Dobrzynski

FTIR study of degradation products of aliphatic polyesters–carbon fibres composites

Abstract Biodegradable polymer composites based on polylactides and polyglycolides constitute a group of materials characterised by good biocompatibility. They are considered in tissue engineering as scaffolds for cells proliferation and controlled tissue regeneration. Two types of biodegradable polymers possessing different chemical structure, molecular weights and crystallinity degrees and two composite materials made up of them and carbon fibres were analysed in this study. The samples were incubated in aqueous media for 8 weeks and analysed by means of Fourier transform infrared spectroscopy in the attenuated total reflection mode (FTIR-ATR). Infrared spectroscopy enabled identification of degradation products and estimation of the influence of carbon fibres on hydrolytic degradation of analysed polymers. Analysis of the infrared spectra showed that hydrolytic degradation process depends on chemical structure, molecular weight and crystallinity of polymers. Catalytic effect of carbon fibres at the initial stage of polymer degradation was observed. Further degradation is dependent on the properties of polymer.

The application of microspheres from the copolymers of lactide and ϵ-caprolactone to the controlled release of steroids

Abstract The microspheres made of the copolymers of lactide and ϵ-caprolactone were used for the controlled release of progesterone and β-estradiol. The copolymers contained 83–94% of l or d,l -lactide. The influence of the microstructure of lactidyl blocks in the copolymer chains on the drug release rate was studied. More uniform release rate was observed in the case of the copolymer derived from d,l -lactide as composed to l -lactide. For the copolymer containing 83–94% of d,l -lactide units the progesterone and β-estradiol release rate in vitro was found to be practically constant within over 40 days. The in vivo studies performed on rats revealed that the period of constant release rate of β-estradiol can be prolonged to about 70 days. The microspheres made of the applied poly-( d,l -lactide-co-ϵ-caprolactone) are the convenient system for long time release of steroids.

Copolymerization of glycolide andε-caprolactone, 2. Random copolymerization in the presence of tin octoate

The copolymerization of glycolide with e-caprolactone was performed in the presence of tin octoate at moderate temperatures (100 and 150°C). The influence of the conditions (comonomer ratio, temperature) on the chain microstructure of the obtained copolymers was examined. Transesterification was found to affect considerably the course of the process. The effect of copolymer composition and chain microstructure on thermal properties was also investigated. A phase separation of glycolidyl and caproyl microblocks was observed. The heat of melting of the crystalline phases was found to be dependent on the length of glycolidyl and caproyl microblocks.

Cytocompatibility of aliphatic polyesters--in vitro study on fibroblasts and macrophages.

A resorbable copolymer of glycolide and L-lactide (PGLA), a terpolymer of glycolide, L-lactide, and epsilon-caprolactone (PGLCL), and a copolymer of glycolide and epsilon-caprolactone (PGCL) were synthesized by ring opening polymerization using zirconium acetylacetonate (Zr(acac)(4)) as an initiator. The structure and physicochemical surface properties of the materials were studied by NMR spectroscopy, gel permeation chromatography, differential scanning calorimetry, X-ray photoelectron spectroscopy, atomic force microscopy, and contact angle measurements. On the basis of contact angle measurements and the Owens-Wendt approach, the surface free energy was calculated. The effect of polymeric films produced by solvent casting on morphology and activity of L929 fibroblasts, and two types of macrophages (macrophages from peritoneal exudates and RAW 264.7 monocytes/macrophages), was analyzed. It was found that viability, adhesion, and morphology of fibroblasts on PGLA were very similar to control glass. On PGLCL more adhering cells were round, while on PGCL only single, poorly spread cells were seen, and their viability was significantly reduced. This may suggest that the interaction of fibroblasts with PGCL was due to its hydrophobicity and a very low polarity. Adhesion and viability of RAW 264.7 cells was significantly enhanced on PGLA but reduced on both PGLCL and PGCL. The increased synthesis/release of chemoattractants and metalloproteinases-2 and -9 was observed in the macrophages from peritoneal exudates cultured on PGLA and PGLCL. The viability of cells decreased in the following order: PGLA > PGLCL > PGCL. It is worth noting that glass transition temperature and susceptibility to mechanical deformation of the polymeric materials also decreased in the same order. It may imply that those physical parameters should be also considered as potential factors affecting cell behavior.

Scaffolds with shape memory behavior for the treatment of large bone defects

The aim of the presented study was preparation, analysis of properties, and in vitro characterization of porous shape-memory scaffolds, designed for large bone defects treatment using minimally invasive surgery approach. Biodegradable terpolymers of l-lactide/glycolide/trimethylene carbonate (LA/GL/TMC) and l-lactide/glycolide/ε-caprolactone (LA/GL/Cap) were selected for formulation of these scaffolds. Basic parameters of shape memory behavior (i.e. recovery ratio, recovery time) and changes in morphology (SEM, average porosity) and properties (surface topography, water contact angle, compressive strength) during shape memory cycle were characterized. The scaffolds preserved good mechanical properties (compressive strength about 0.7 to 0.9 MPa) and high porosity (more than 80%) both in initial shape as well as after return from compressed shape. Then the scaffolds in temporary shape were inserted into the model defect of bone tissue at 37°C. After 12 min the defect was filled completely as a result of shape recovery process induced by body temperature. The scaffold obtained from LA/GL/TMC terpolymer was found the most prospective for the planned application thanks to its appropriate recovery time, high recovery ratio (more than 90%), and cytocompatibility in contact with human osteoblasts and chondrocytes.

Bioresorbable terpolymers based on L-lactide, glycolide and trimethylene carbonate with shape memory behaviour

This paper presents the course of synthesis and the properties of biodegradable terpolymers obtained by ROP of L-lactide with glycolide, catalysed with zirconium(IV) acetylacetonate and conducted in the presence of a macroinitiator – trimethylene carbonate oligomers terminated with hydroxyl groups. The oligomers were also prepared by ROP reaction of TMC catalysed by zinc(II) acetylacetonate monohydrate in the presence of polyols as initiators. Depending on the type of initiator used, the oligomers had a linear or branched structure of the chain with different hydroxyl end-groups. Some of the obtained oligomers formed a network. The effect of the terpolymer chain structure on mechanical and thermomechanical properties as well as shape-memory behaviour was shown. The ability to control the speed of return from a temporary to a permanent shape, the value of stress of return triggered by this phenomenon, and the magnitude of the temperature range in which the phenomenon took place through appropriate selection of conditions for programming the temporary shape or/and terpolymer chain microstructure has been shown. The possibility of adjusting these parameters as presented in this paper is vital in the process of designing a bioresorbable material, which can be used for forming self-expanding stents or self-clamping surgical staples.

Poly(L‐lactide‐co‐glycolide) scaffolds coated with collagen and glycosaminoglycans: Impact on proliferation and osteogenic differentiation of human mesenchymal stem cells

In this study, we analyzed poly(L-lactide-co-glycolide) (PLGA) scaffolds modified with artificial extracellular matrices (aECM) consisting of collagen type I, chondroitin sulphate, and sulphated hyaluronan (sHya). We investigated the effect of these aECM coatings on proliferation and osteogenic differentiation of human mesenchymal stem cells (hMSC) in vitro. We found that scaffolds were homogeneously coated, and cross-linking of aECM did not significantly influence the amount of collagen immobilized. Cell proliferation was significantly increased on cross-linked surfaces in expansion medium (EM), but was retarded on cross-linked and non-cross-linked collagen/sHya coatings. The alkaline phosphatase activity was increased on sHya-containing coatings in EM even without the presence of differentiation supplements, but was six to ten times higher in differentiation medium (DM) and comparable for cross-linked and non-cross-linked collagen/sHya. The highest amount of calcium phosphate mineral was deposited on day 28 on cross-linked collagen/sHya. Therefore, coatings of PLGA scaffolds with collagen/sHya promoted the osteogenic differentiation of hMSCs in vitro and might be an interesting candidate for the modification of PLGA for bone reconstruction in vivo.

Double layer paclitaxel delivery systems based on bioresorbable terpolymer with shape memory properties.

The growing interest in the bioresorbable polymers contributed to developing a number of commercially available controlled drug delivery systems. Due to a variety of drugs and their physicochemical properties, there is a necessity of choosing an appropriate drug carrier. Terpolymer with shape memory properties was used to obtain double layer matrices composed of drug free matrix and paclitaxel containing layer. The in vitro degradation and drug release study were conducted at 37 °C in PBS (pH 7.4). The investigated materials were characterized by GPC (gel permeation chromatography) and DSC (differential scanning calorimetry). HPLC (high-pressure liquid chromatography) was applied to analyze the amount of released paclitaxel. The main purpose of this work was to determine the usefulness of the studied terpolymer as an anti-restenotic drug vehicle. Based on the obtained results it was established that polymers degradation proceeded regularly and provided even paclitaxel release profiles. Double layer systems allowed to modify the amount of released drug which may be considered while developing the self-expanding drug-eluting stents tailoring different clinical indications.

Designing bioresorbable polyester matrices for controlled doxorubicin release in glioma therapy.

The influence of the chain microstructure on release process of doxorubicin from polymeric matrices was analyzed. Aliphatic polyester copolymers with optimal chain microstructure, i.e. poly(glycolide-co-L-lactide, 15/85) (PGLA) and poly(glycolide-co-epsilon-caprolactone, 10/90) (PGCA) were synthesized for long-term doxorubicin delivery systems. Various release profiles from PGLA and PGCA matrices were obtained. The investigations revealed the most steadily doxorubicin release from PGCA matrices with 5% (w/w) of drug content. Degradation of matrices with and without drug was monitored by means of NMR spectroscopy and confirmed stability of degradation process. From PGCA matrices the increase of released doxorubicin amount was observed during first 60 days. On the contrary in case of matrices obtained from PGLA the delay of doxorubicin release was observed during first 50 days, what was caused by interaction of drug molecules with polylactide chain of polymer matrix. The interaction between doxorubicin molecules and polylactide chains was confirmed by IR spectroscopy. This fact can be used for designing of delivery systems consisting of combination of matrices with different microstructure of copolymer chains in order to adjust concentration of released doxorubicin and stabilization of drug release process.

The Influence of Chain Microstructure of Biodegradable Copolyesters Obtained with Low-Toxic Zirconium Initiator to In Vitro Biocompatibility

Because of the wide use of biodegradable materials in tissue engineering, it is necessary to obtain biocompatible polymers with different mechanical and physical properties as well as degradation ratio. Novel co- and terpolymers of various composition and chain microstructure have been developed and applied for cell culture. The aim of this study was to evaluate the adhesion and proliferation of human chondrocytes to four biodegradable copolymers: lactide-coglycolide, lactide-co-ε-caprolactone, lactide-co-trimethylene carbonate, glycolide-co-ε-caprolactone, and one terpolymer glycolide-colactide-co-ε-caprolactone synthesized with the use of zirconium acetylacetonate as a nontoxic initiator. Chain microstructure of the copolymers was analyzed by means of 1H and 13C NMR spectroscopy and surface properties by AFM technique. Cell adhesion and proliferation were determined by CyQUANT Cell Proliferation Assay Kit. After 4 h the chondrocyte adhesion on the surface of studied materials was comparable to standard TCPS. Cell proliferation occurred on all the substrates; however, among the studied polymers poly(L-lactide-coglycolide) 85 : 15 that characterized the most blocky structure best supported cell growth. Chondrocytes retained the cell membrane integrity evaluated by the LDH release assay. As can be summarized from the results of the study, all the studied polymers are well tolerated by the cells that make them appropriate for human chondrocytes growth.