PubMed Health⌕ Search

Biomedical subjects

L van der Does

Publications and source records attributed to L van der Does.

16 recordsLinked to original sources

In vivo testing of crosslinked polyethers. I. Tissue reactions and biodegradation.

The in vivo biocompatibility and biodegradation of cross-linked (co)polyethers with and without tertiary hydrogen atoms in the main chain and differing in hydrophilicity were studied by means of subcutaneous implantation in rats. After 4 days, 1 month, and 3 months postimplantation, the tissue reactions and interactions were evaluated by light microscopy (LM) and transmission electron microscopy (TEM). Poly(tetrahydrofuran) (poly(THF)), poly(propylene oxide) (poly(POx)), and poly(tetrahydrofuran-co-oxetane) (poly-(THF-co-OX)) were tested as relatively hydrophobic polyethers, and poly(ethylene oxide) (PEO) and a poly(THF)/ PEO blend were used as more hydrophilic materials. In general, all polyethers showed good biocompatibility with respect to tissue reactions and interactions, with low neutrophil and macrophage infiltration, a quiet giant cell reaction, and formation of a thin fibrous capsule. For the relatively hydrophobic polyethers studied, the biostability increased in the order poly(POx) < poly(THF-co-OX) < poly(THF), probably indicating that the absence of tertiary hydrogen atoms has a positive effect on the biostability. Concerning the more hydrophilic materials, crosslinked PEO showed the highest rate of degradation, probably due to the mechanical weakness of the hydrogel in combination with the highest presence of giant cells as a result of the high porosity. A frayed surface morphology was observed after implantation of the crosslinked poly(THF)/PEO blend, which might be due to preferential degradation of PEO domains.

Animals↗

In vivo testing of crosslinked polyethers. II. Weight loss, IR analysis, and swelling behavior after implantation.

As reported in Part I ("In vivo testing of crosslinked polyethers. I. Tissue reactions and biodegradation," J. Biomed. Mater. Res., this issue, pp. 307-320), microscopical evaluation after implantation of crosslinked (co)polyethers in rats showed differences in the rate of biodegradation, depending on the presence of tertiary hydrogen atoms in the main chain and the hydrophilicity of the polyether system. In this article (Part II) the biostability will be discussed in terms of weight loss, the swelling behavior, and changes in the chemical structure of the crosslinked polyethers after implantation. The biostability increased in the order poly(POx) < poly(THF-co-OX) < poly(THF) for the relatively hydrophobic polyethers. This confirmed our hypothesis that the absence of tertiary hydrogen atoms would improve the biostability. On the other hand, signs of biodegradation were observed for all polyether system studied. Infrared surface analysis showed that biodegradation was triggered by oxidative attack on the polymeric chain, leading to the formation of carboxylic ester and acid groups. It also was found that in the THF-based (co)polyethers, alpha-methylene groups were more sensitive than beta-methylene groups. For a hydrophilic poly(THF)/PEO blend, an increase in surface PEO content was found, which might be due to preferential degradation of the PEO domains.

Animals↗

Iron removal from milk and other nutrient media with a chelating resin.

A water-insoluble iron(III)-chelating resin was used to study iron removal from milk and other nutrient media. Seventy to 85% of the iron could be removed from wine and beer with the resin, which was a crosslinked copolymer of 1-(beta-acrylamidoethyl)-3-hydroxy-2-methyl-4(1H)- pyridinone and N,N-dimethylacrylamide. Iron removal from milk was dependent on the pH of milk and on the concentration of soluble chelators added. Under the same conditions as used for the removal of iron from wine and beer, only 11 to 19% of the iron could be removed from milk. However, in combination with water-soluble chelators, the resin removed 60 to 75% of the iron from the milk. Preliminary results showed that the growth of spores of Clostridium tyrobutyricum in the treated milk was reduced. Moreover, addition of the resin and sodium bicarbonate to the milk completely inhibited the growth of the spores.

Acrylamides↗

Preparation of apolactoferrin with a very low iron saturation.

Iron(III) removal from lactoferrin by an iron(III)-chelating resin with immobilized 3-hydroxy-2-methyl-4(1H)-pyridinone ligands was studied at physiological pH in the presence of citrate. The resin had a marked effect on the extent of iron removal. By using the iron(III)-chelating resin, removal of iron from lactoferrin was nearly complete in < 24 h. Apolactoferrin with 4% iron saturation could be prepared conveniently from 100% or from 18% iron-saturated lactoferrin under mild conditions without affecting the iron-binding capacity of the protein. The iron saturation of the obtained apolactoferrin was much lower than that of the apolactoferrin prepared by reported methods.

Apoproteins↗

Iron(III)-chelating resins. IX. Antibacterial activity of a water-insoluble iron(III)-chelating resin.

Antibacterial activity of a water-insoluble iron(III)-chelating resin with covalently bonded 3-hydroxy-2-methyl-4(1H)-pyridinone (HMP) groups was evaluated in a brain heart infusion (BHI) medium. The activity of the resin against Escherichia coli was lower than that of soluble HMP iron(III) chelators, whereas against Listeria inocua, an activity approximately equal to those of the soluble chelators was found. It was observed that the growth of E. coli and L. inocua was reduced by increasing the amounts of the resin from 2 to 40 mg of resin/mL of medium. Inhibition of bacterial growth in the presence of the resin (10 mg/mL) was abolished by addition of ferric ion to the medium, indicating that the growth of E. coli and L. inocua was dependent on the available iron in the medium. Reducing the iron concentration in the medium from 14.2 to 0.16 microM (by action of the resin) resulted in a decrease in the growth response from 100% to 19% for E. coli and from 100% to 10% for L. inocua. In addition, the influence of citrate was studied, but only small effects of citrate supplementation on the growth of bacteria and on the antibacterial activity of the resin were observed.

Acrylamides↗

Iron (III)-chelating resins. 3. Synthesis, iron (III)-chelating properties, and in vitro antibacterial activity of compounds containing 3-hydroxy-2-methyl-4(1H)-pyridinone ligands.

The synthesis, iron (III)-chelating properties, and antibacterial activity of several compounds containing the 3-hydroxy-2-methyl-4(1H)-pyridinone (HMP) moiety are described. Using the HMP derivatives iron (III) could be mobilized from iron (III)-binding proteins at physiological pH with a rate order of transferrin > lactoferrin > ferritin. Addition of HMP-containing compounds to a growth medium at a concentration of 20 mM/L resulted in a complete inhibition of the growth of Escherichia coli and about 90% inhibition for Listeria inocua after 7 h of incubation at 37 degrees C. After inhibition of bacteria growth by the HMP derivatives growth started again when ferric ions were added to the medium, which implies that the antibacterial activity is due to a limitation of iron available to the organisms.

Anti-Bacterial Agents↗

Tetrahydrofuran (co)polymers as potential materials for vascular prostheses.

Polyethers were studied as potential materials for vascular prostheses. By crosslinking poly(tetramethylene oxide)(PTMO) with poly(ethylene oxide)(PEO), hydrophilic networks were obtained containing PTMO as well as PEO. Attempts were made to reduce the crystallinity and melting point of PTMO because of the required elastomeric behaviour at body temperature. Compared to non-crosslinked PTMO, crosslinking in the melt resulted in a decrease in the melting point from 43.7 to 38.4 degrees C and a decrease of the crystallinity from 46 to 28%. By copolymerizing tetrahydrofuran with oxetane or dimethyloxetane, melting points below 38 degrees C were obtained, together with crystallinities lower than 20%.

Biocompatible Materials↗

Iron(III) chelating resins II. 3-Hydroxy-4(1H)-pyridinones-sepharose gels.

3-Hydroxy-4(1H)-pyridinones(HP)-Sepharose gels were prepared to study their iron(III) chelating properties. As ligands, derivatives of 3-hydroxy-4(1H)-pyridinone were coupled to CNBr-activated Sepharose gels. HP-Sepharose gels were obtained with HP densities of 23-28 mumol/ml gel and iron(III) chelating capacities of 19-23 mumol/ml gel at pH 6.8. From preliminary experiments, it was found that with the gels 19-27% iron could be removed from milk. In addition, 74% of iron(III) was removed from 100% iron(III) saturated lactoferrin within 24 h at pH 6.8 in the presence of citrate and a Sepharose gel, onto which 1-(2-aminoethyl)-3-hydroxy-2-methyl-4(1H)-pyridinone had been immobilized as a ligand. The properties of the gels make them potentially useful as water-insoluble iron(III) chelating agents.

Animals↗

Iron(III) chelating resins--I. Preparation and properties of Sepharose-desferrioxamine gels.

For the removal of iron(III), Sepharose-desferrioxamine gels were prepared by the coupling of CNBr-activated Sepharose with desferrioxamine (DFO) at pH 7.8-8.3. DFO densities of the gels were 12-23 mumol/ml gel with iron(III) chelating capacities of 8.5-18 mumol/ml gel. The Sepharose-DFO gels with a high affinity for iron(III) were used for the removal of iron(III) from aqueous iron(III) solutions, wine, milk and whey.

Animals↗

Poly(vinyl alcohol)-heparin hydrogels as sensor catheter membranes.

Poly(vinyl alcohol)-heparin hydrogels with varying water content were synthesized for use as sensor catheter membranes. Films were cast from aqueous mixtures of poly(vinyl alcohol) (PVA), a photosensitive cross-linker p-diazonium diphenyl amine polymer (PA), glutaraldehyde (GA) and heparin. After drying, the films were cross-linked by successive UV irradiation and heat treatment. To get an indication about the cross-linking density of the networks, the water content of the hydrogels was measured after equilibration in water. Hydrogels from PVA, PA, GA and heparin, with a water content of 35-95%, could be obtained if the components were dissolved in saline instead of water. The release of heparin from PVA-heparin or PVA-PA-heparin hydrogels was studied using different receiving phases. The cumulative amount of released heparin appeared to be dependent on the initial water content of the hydrogels and the composition of the receiving phase. For the PVA-PA-heparin hydrogels as well as the PVA-heparin hydrogels the cumulative amount of released heparin in water was about six times higher than in a Tris buffer. Using Tris buffer as receiving phase PVA-PA-heparin hydrogels with water contents of 53, 61 or 71% released heparin for at least 3 wk. The cumulative amount of released heparin increased with initial water content of these hydrogels. Recalcification times (RCT) of plasma exposed to PVA-PA-heparin hydrogels (water content 53%), which released heparin at a low rate (2 micrograms/cm2 per day), were markedly prolonged compared with the RCT values for PVA-PA hydrogels without heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

Platelet deposition studies on copolyether urethanes modified with poly(ethylene oxide).

Pellethane 2363 80A films and tubings were chemically modified and the effect of these modifications on platelet deposition was studied. Grafting of high molecular weight poly(ethylene oxide) and graft polymerization of methoxy poly(ethylene glycol) 400 methacrylate resulted in surfaces with a good water wettability. The increased hydrophilicity of these modified surfaces could be demonstrated by contact angle measurements. The platelet deposition was investigated with tubings in a capillary flow system, using different types of perfusates. Platelet deposition from a buffer-containing perfusate on surfaces modified with either high molecular weight poly(ethylene oxide) or methoxy poly(ethylene glycol) 400 methacrylate was almost absent and less than on Pellethane 2363 80A. Using a citrated plasma-containing perfusate the amount of deposited platelets on Pellethane 2363 80A modified with high molecular weight poly(ethylene oxide) was low and about the same as on unmodified surfaces. However, a marked reduced platelet deposition compared to unmodified Pellethane 2363 80A was found when the platelets were activated by Ca2+ ionophore. The improved blood compatibility of the modified Pellethane 2363 80A tubings obviously indicates the favourable effect of the presence of grafted PEO on the surface.

Biocompatible Materials↗

Surface modification of copolyether-urethane catheters with poly(ethylene oxide).

Pellethane 2363 80A catheters were modified with poly(ethylene oxide) in order to improve their blood compatibility. Contact angle measurements showed that Pellethane 2363 80A surfaces had increased wettability after this modification. The results of in vitro blood compatibility tests showed that surface modification with poly(ethylene oxide) resulted in a five-fold reduction of platelet deposition. Activation of coagulation was not affected.

Biocompatible Materials↗

Small diameter blood vessel prostheses from blends of polyethylene oxide and polypropylene oxide.

Studies on the relationship between blood platelet adhesion and type and amount of polyether segments in copolyetherurethanes report a reduced platelet adhesion with increasing polyether content. We therefore assumed that combinations of polyethylene oxide (PEO) and polypropylene oxide (PPOX) might give materials with a good blood compatibility. Water-soluble PEO was attached to PPOX by u.v.-initiated crosslinking. Films were tested for hydrophilicity, mechanical properties, protein adsorption and blood compatibility. The hydrophilicity was determined by swelling experiments. A compromise between hydrophilicity (PEO) and mechanical strength (PPOX) was met at a swelling of 0.5 (PPOX/PEO ratio: 90/10). In protein adsorption studies only small amounts of adsorbed proteins were found. Three blood material interaction in vitro tests gave good results: a low platelet adhesion and kallikrein generation and a high APTT value. Porous tubings (inner diameter 1.3 mm) were fabricated, by spinning from solution, for implantation in the abdominal aorta of rats. Stress-strain diagrams were comparable to those reported for natural blood vessels.

Adsorption↗

Grafting of a synthetic heparinoid polyelectrolyte onto silicone rubber.

Using a [3H]-labelled polyelectrolyte as a tracer, the 60Co grafting of a synthetic heparinoid polyelectrolyte onto silicone rubber was studied. The polyelectrolyte was labelled by the coupling of a radioactive amine to carboxylate groups of the polyelectrolyte. The amount of grafted polyelectrolyte was found to be dependent on the radiation dose.

Adsorption↗

Hydrogels by irradiation of a synthetic heparinoid polyelectrolyte.

Gamma irradiation of aqueous solutions of a synthetic heparinoid polyelectrolyte results in the formation of hydrogels, varying in water content and mechanical strength. The equilibrium water content and the mechanical strength of the hydrogels are dependent on the initial polyelectrolyte concentration, the molecular weight of the polyelectrolyte, the percentage of double bonds in the polyelectrolyte and the radiation dose. The polyelectrolyte hydrogels do not deplete Antithrombin III from blood and there is no activation of factor XII according to an in vitro kallikrein generation test. However, in a very sensitive test for factor XII activation (contact promoted shortening of the thrombotest) a slight activation of this factor was observed.

Biocompatible Materials↗

Anticoagulant activity of a synthetic heparinoid in relation to molecular weight and N-sulfate content.

Addition of chlorosulfonyl isocyanate to C==C bonds in cis-1,4-polyisoprene and reaction of the adduct with NaOH resulted in the formation of a water-soluble polyelectrolyte with N-sulfate and carboxylate groups. The polyelectrolyte showed anticoagulant activity and it was found, just as with heparin, that the activity was related to molecular weight and N-sulfate content.

Blood Coagulation↗