Biomedical subjects

D W Grijpma

Publications and source records attributed to D W Grijpma.

11 recordsLinked to original sources

PubMed2001

The different behaviors of skeletal muscle cells and chondrocytes on PEGT/PBT block copolymers are related to the surface properties of the substrate.

The attachment, proliferation, morphology, and differentiation of two cell types-skeletal muscle cells and chondrocytes-were investigated on different compositions of poly(ethylene glycol) and poly(butylene terephthalate) segmented block copolymers. Four weight percentages (40, 55, 60, and 70%) and two different molecular weights (300 and 1000 Da) of poly(ethylene glycol) were tested. Varying the weight percentage and molecular weight of poly(ethylene glycol) resulted in different behaviors for skeletal muscle cells and chondrocytes. The attachment of skeletal muscle was the highest (similar to tissue culture polystyrene) when copolymers containing 55 wt % of poly(ethylene glycol) were used, regardless of the poly(ethylene glycol) molecular weight. Maximum proliferation and differentiation of skeletal muscle cells was achieved when copolymers containing 55 wt % and 300 Da molecular weight of poly(ethylene glycol) were used. In contrast, the weight percentage and molecular weight of poly(ethylene glycol) had no significant effect on chondrocyte attachment and proliferation; the attached chondrocytes retained a differentiated phenotype only when a 70 wt % of poly(ethylene glycol) was used. Cell behavior was correlated with the surface properties of the copolymer films, as indicated by contact-angle measurements. These results suggest that an optimized wt % and molecular weight of poly(ethylene glycol) will be useful depending on the specific cell type.

Animals↗

PubMed2001

Antimicrobial effects of positively charged surfaces on adhering Gram-positive and Gram-negative bacteria.

The infection of biomaterials is determined by an interplay of adhesion and surface growth of the infecting organisms. In this study, the antimicrobial effects on adhering bacteria of a positively charged poly(methacrylate) surface (xi potential +12 mV) were compared with those of negatively charged poly(methyl methacrylate) (-12 mV) and a highly negatively charged poly(methacrylate) (-18 mV) surface. Initial adhesion of Staphylococcus aureus ATCC 12600, Staphylococcus epidermidis HBH(2) 102, Escherichia coli O2K2 and Pseudomonas aeruginosa AK1 to these surfaces was measured in a parallel plate flow chamber in phosphate-buffered saline. Adhering bacteria were allowed to multiply by perfusing the flow chamber with growth medium. All bacteria adhered most rapidly to the positively charged surface, but there was no subsequent surface growth of the Gram-negative strains. On the negatively charged surfaces, despite a slower initial adhesion, surface growth of the adhering bacteria was exponential for both Gram-positive and Gram-negative strains. These results suggest that positively charged biomaterial surfaces exert an antimicrobial effect on adhering Gram-negative bacteria, but not on Gram-positive ones.

Bacterial Adhesion↗

PubMed2001

Copolymers of trimethylene carbonate and epsilon-caprolactone for porous nerve guides: synthesis and properties.

Copolymers of trimethylene carbonate and epsilon-caprolactone were synthesized and characterized with the aim of assessing their potential in the development of a flexible and slowly degrading artificial nerve guide for the bridging of large nerve defects. The effect of the monomer ratio on the physical properties of the polymers and its influence on the processability of the materials was investigated. Under the applied polymerization conditions (130 degrees C, 3 days using stannous octoate as a catalyst) high molecular weight polymers (Mn above 93 000) were obtained. All copolymers had glass transition temperatures below room temperature. At trimethylene carbonate contents higher than 25 mol% no crystallinity was detected. A decrease in crystallinity resulted in the loss of strength and decrease in toughness, as well as in an increased polymer wettability. Amorphous poly(trimethylene carbonate), however, showed excellent ultimate mechanical properties due to strain-induced crystallization (Tm = 36 degrees C). Low crystallinity copolymers could be processed into dimensionally stable porous structures by means of immersion precipitation and by combination of this technique with the use of porosifying agents. Porous membranes of poly(trimethylene carbonate) could be prepared when blended with small amounts of high molecular weight poly(ethylene oxide). Poly(trimethylene carbonate) and poly(trimethylene carbonate-co-epsilon-caprolactone) copolymers with high epsilon-caprolactone content possess good physical properties and are processable into porous structures. These materials are most suitable for the preparation of porous artificial nerve guides.

Biocompatible Materials↗

PubMed2000

In vivo and in vitro degradation of poly[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL], and the implications for the use in nerve reconstruction.

Nerve guides can be used for the reconstruction of peripheral nerve defects. After serving their function, nerve guides should degrade. p[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL] degrades completely within 1 year without the formation of a slow degrading crystalline fraction. Although the tensile strength (TS) of a p[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL] nerve guide is negligible after 2 months, nerve regeneration across a 1-cm gap in the sciatic nerve of the rat is faster and qualitatively better than after reconstruction using autologous nerve grafts. During degradation p[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL] swells, especially during the first 3 months. This can have a negative influence on the regenerating nerve. p[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL] nerve guides could only be used in the clinical situation in case of short nerve gaps (several mm) in small nerves (for instance digital nerves). Refinements will be needed to successfully reconstruct longer nerve gaps (several cm).

Animals↗

PubMed2000

Microspheres for protein delivery prepared from amphiphilic multiblock copolymers. 2. Modulation of release rate.

Amphiphilic multiblock copolymers, based on hydrophilic poly(ethylene glycol) (PEG) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks were used as matrix material for protein-loaded microspheres. The efficiency of lysozyme entrapment by a double emulsion method was found to depend on the swelling behavior of the polymers in water and decreased from 100% for polymers with a degree of swelling of less than 1.8 to 11% for PEG-PBT copolymers with a degree of swelling of 3.6. The particle size could be controlled by varying the concentration of the polymer solution used in the microsphere preparation. An increase in the polymer concentration resulted in a proportional increase in the particle size. The in vitro release profiles of the encapsulated model protein lysozyme could be precisely tailored by variation of the copolymer composition and the size of the microspheres. Both a slow continuous release of lysozyme, and a fast release which was completed within a few days could be obtained. The release behavior, attributed to a combination of diffusion and polymer degradation, could be described by a previously developed model.

Algorithms↗

PubMed2000

Microspheres for protein delivery prepared from amphiphilic multiblock copolymers. 1. Influence of preparation techniques on particle characteristics and protein delivery.

The entrapment of lysozyme in amphiphilic multiblock copolymer microspheres by emulsification and subsequent solvent removal processes was studied. The copolymers are composed of hydrophilic poly(ethylene glycol) (PEG) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks. Direct solvent extraction from a water-in-oil (w/o) emulsion in ethanol or methanol did not result in the formation of microspheres, due to massive polymer precipitation caused by rapid solvent extraction in these non-solvents. In a second process, microspheres were first prepared by a water-in-oil-in-water (w/o/w) emulsion system with 4% poly(vinyl alcohol) (PVA) as stabilizer in the external phase, followed by extraction of the remaining solvent. As non-solvents ethanol, methanol and mixtures of methanol and water were employed. However, the use of alcohols in the extraction medium resulted in microspheres which gave an incomplete lysozyme release at a non-constant rate. Complete lysozyme release was obtained from microspheres prepared by an emulsification-solvent evaporation method in PBS containing poly(vinyl pyrrolidone) (PVP) or PVA as stabilizer. PVA was most effective in stabilizing the w/o/w emulsion. Perfectly spherical microspheres were produced, with high protein entrapment efficiencies. These microspheres released lysozyme at an almost constant rate for approximately 28 days. The reproducibility of the w/o/w emulsion process was demonstrated by comparing particle characteristics and release profiles of three batches, prepared under similar conditions.

Drug Compounding↗

PubMed2000

Control of protein delivery from amphiphilic poly(ether ester) multiblock copolymers by varying their water content using emulsification techniques.

Protein-containing films and microspheres, based on poly(ethylene glycol)-poly(butylene terephthalate) (PEG-PBT) multiblock copolymers, were prepared from water-in-oil (w/o) emulsions. The properties of the matrices could be controlled by the water-to-polymer ratio (w/p) in the w/o emulsion. A linear increase in water uptake of the matrices was observed with increasing emulsion w/p. This could be explained by an increase in the number of dispersed water-rich domains in the polymer matrix. At low volume fraction of the dispersed phase (epsilon), lysozyme release was mainly dependent on the permeability of the swollen polymer bulk. Above a critical volume fraction (the percolation threshold epsilon(c)), the dispersed water-rich phase formed an interconnected network, which largely enhanced the permeability of the matrix. Determination of the permeability of PEG-PBT matrices for vitamin B(12) as a function of epsilon confirmed the formation of such an interconnected network. This interconnected network could be used to achieve controlled release of a large protein (bovine serum albumin, BSA) from PEG-PBT films and microspheres. Due to its hydrodynamic diameter, BSA was screened by the polymer network when epsilon was low. However above epsilon(c), the fraction released BSA increased with increasing volume fraction of the dispersed phase. A very rapid BSA release could be obtained, with the majority of the incorporated BSA released within 1 day, as well as a slow and continuous release, lasting for over 150 days. When BSA-containing microspheres were prepared with a volume fraction just below the percolation threshold, a delayed release was observed. This was attributed to the effect of polymer degradation on matrix permeability.

Drug Delivery Systems↗

PubMed2000

Zero-order release of lysozyme from poly(ethylene glycol)/poly(butylene terephthalate) matrices.

Protein release from a series of biodegradable poly(ether ester) multiblock copolymers, based on poly(ethylene glycol) (PEG) and poly(butylene terephthalate) (PBT) was investigated. Lysozyme-containing PEG/PBT films and microspheres were prepared using an emulsion technique. Proteins were effectively encapsulated and dense polymer matrices were formed. The swelling in water of PEG/PBT films reached equilibrium within 3 days. The degree of swelling increased with increasing PEG content and with increasing molecular weight of the PEG segment. The release rate of lysozyme from PEG/PBT films could be tailored very precisely by controlling the copolymer composition. Release rates increased with increasing PEG/PBT weight ratio and increasing molecular weight of the PEG segment. For films prepared from block copolymers with PEG blocks of 4000 g/mol, first-order lysozyme release was observed. For matrices prepared from polymers with PEG segments of 1000 and 600 g/mol, the lysozyme release profile followed near zero-order kinetics. A mathematical description of the release mechanism was developed which takes into account the effect of polymer hydrolytic degradation on solute diffusion. The model was found to be consistent with the experimental observations. Finally, determination of the activity of released protein showed that lysozyme was not damaged during the formulation, storage and release periods.

Drug Stability↗

PubMed2000

Amphiphilic poly(ether ester amide) multiblock copolymers as biodegradable matrices for the controlled release of proteins.

Amphiphilic poly(ether ester amide) (PEEA) multiblock copolymers were synthesized by polycondensation in the melt from hydrophilic poly(ethylene glycol) (PEG), 1,4-dihydroxybutane and short bisester-bisamide blocks. These amide blocks were prepared by reaction of 1,4-diaminobutane with dimethyl adipate in the melt. A range of multiblock copolymers were prepared, with PEG contents varying from 23-66 wt %. The intrinsic viscosity of the PEEA polymers varied from 0.58-0.78. Differential scanning calorimetry showed melting transitions for the PEG blocks and for the amide-ester blocks, suggesting a phase separated structure. Both the melting temperature and the crystallinity of the hard amide-ester segments decreased with increasing PEG content of the polymers. The equilibrium swelling ratio in phosphate buffered saline (PBS) increased with increasing amount of PEG in the polymers and varied from 1.7 to 3.7, whereas the polymer that contained 66 wt % PEG was soluble in PBS. During incubation of PEEA films in PBS, weight loss and a continuous decrease in the resulting inherent polymer viscosity was observed. The rate of degradation increased with increasing PEG content. The composition of the remaining matrices did not change during degradation. A preliminary investigation of the protein release characteristics of these PEEA copolymers showed that release of the model protein lysozyme was proportional to the square root of time. The release rate was found to increase with increasing degree of swelling of the polymers.

Biocompatible Materials↗

PubMed1999

A controlled release system for proteins based on poly(ether ester) block-copolymers: polymer network characterization.

The properties of a series of multiblock copolymers, based on hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(butylene terephthalate) (PBT) blocks were investigated with respect to their application as a matrix for controlled release of proteins. The degree of swelling, Q, of the copolymers increased with increasing PEG content and with increasing molecular weight of the PEG segment. Within the composition range tested, Q varied from 1.26 for polymers with PEG segments of 600 g/mol and a PBT content of 60 weight.% up to 3.64 for polymers with PEG segments of 4000 g/mol and a PEG/PBT weight ratio of 80:20. Equilibrium stress (compression)-strain measurements were performed in order to estimate mesh sizes. The mesh size of the copolymers ranged from 38 to 93 A, which was experimentally confirmed by diffusion of vitamin B(12) (hydrodynamic diameter d(h)=16.6 A), lysozyme (d(h)=41 A) and bovine serum albumin (d(h)=72 A). The in vitro degradation of PEG/PBT copolymers with a PEG block length of 1000 g/mol and PEG/PBT weight ratios of 70:30, 60:40 and 40:60 was studied. Matrices with increasing PEG contents exhibited a faster weight loss in phosphate-buffered saline (pH 7.4) at 37 degrees C. Over a degradation period of 54 days, M(n) decreased by about 35-45%, while the composition of the matrices, determined by NMR, remained almost constant.

Animals↗

PubMed1995

High-impact poly(L/D-lactide) for fracture fixation: in vitro degradation and animal pilot study.

The impact strength of amorphous lactide copolymers can be significantly improved by blending with biodegradable rubbers. Rubber toughening of amorphous poly(85L/15D -lactide) with the copolymer poly (50/50-trimethylenecarbonate-co-epsilon-caprolactone) results in a high-impact polymer (PDLLA/P(TMC-CL)). In vitro, the PDLLA/P(TMC-CL) blend retained its tensile and impact strength for a long period of time. Up to 45 weeks, the amount of water absorbed by the blend remained very low and no significant mass loss was observed. To test the suitability for fracture fixation, in a dog study mandibular fractures were fixated with PDLLA/P(TMC-CL) bone plates and screws. Bone healing was uneventful without premature failure of the implants. Although long-term degradation studies have to be carried out, PDLLA/P(TMC-CL) seems to be promising for application in fracture fixation.

Animals↗