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Biomedical subjects

G R Llanos

Publications and source records attributed to G R Llanos.

3 recordsLinked to original sources

Immobilization of poly(ethylene glycol) onto a poly(vinyl alcohol) hydrogel: 2. Evaluation of thrombogenicity.

Immobilized polyethylene glycol (PEG) reduced the amount of bovine serum albumin (BSA) adsorbed on polyvinyl alcohol (PVA) hydrogel, but did not reduce the platelet reactivity of the hydrogel surface. PEG, molecular weight (MW) 2000 or 5000, with or without a monomethoxy end group, was covalently bound to glutaraldehyde-crosslinked PVA either through a cyclic acetal or an urethane functional group with a surface coverage of 70% (as measured by x-ray photoelectron spectroscopy [XPS]). Immobilization of monomethoxy-PEG via a cyclic acetal reduced BSA adsorption to PVA from 11 +/- 2 nmol/m2 to 3.9 +/- 0.3 nmol/m2 and 3.3 +/- 0.3 nmol/m2 for MW 2000 and 5000, respectively. Similarly, urethane bound PEG reduced adsorption to 3.5 +/- 1.6 nmol/m2 for MW 2000 and 5.4 +/- 1.0 nmol/m2 for MW 5000. Whole blood clotting times of PVA (using a Chandler loop) were not affected by covalently linked PEG, although the initial rate of thrombin generation at the surface, measured using a fluorogenic substrate, was marginally reduced; a rate constant of 4.2 +/- 0.1 cm/sec and 3.5 +/- 0.1 cm/sec were obtained for MW 2000 and 5000, respectively, compared to 5.6 +/- 1.0 cm/sec for PVA. Ex vivo evaluation using a canine arteriovenous shunt revealed that the hydrogel, with or without bound PEG, reduced circulating platelet levels by 35-70% after 4 days. The initial fractional rate of platelet destruction determined from measurement of platelet cyclooxygenase activity, indicated that cyclic acetal or urethane bound PEG of either molecular weight had no effect on platelet consumption produced by PVA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗

Does polyethylene oxide possess a low thrombogenicity?

Because of the 'bland' nature of polyethylene oxide towards proteins and cells, considerable effort has been devoted to preparing surfaces rich in polyethylene oxide, using block copolymers, surface immobilization or other methods. It is clear that these modifications result in reduced levels of cell (including platelet) adhesion and protein adsorption, when compared to unmodified and typically hydrophobic substrates. It is far less clear whether the reduced adhesion or adsorption is due specifically to the thermodynamic effects of polyethylene oxide or to the increase in surface hydrophilicity after its immobilization. Even more so, it is unclear whether the reduction in such parameters is evidence of a reduced thrombogenicity.

Animals↗

Heparin-poly(ethylene glycol)-poly(vinyl alcohol) hydrogel: preparation and assessment of thrombogenicity.

Heparin was immobilized on to poly(vinyl alcohol) hydrogel (PVA) through the free isocyanate end-group on a poly(ethylene glycol) (PEG2000) which had been previously covalently linked to the hydrogel via a urethane moiety. The intention was to reduce the platelet reactivity of the PVA while also suppressing fibrin formation. Elemental nitrogen analysis revealed that the total amount of bound heparin was 19 +/- 7 mumol/g of dried gel. An increase in the in vitro whole blood clotting time of PVA was observed. This was attributed to bound heparin, as the elution rate of heparin from the gel (23 pmol/m2 min) was too low to produce a significant bulk concentration to interfere with fibrin formation. Ex vivo assessment using a chronic canine A-V shunt showed that the bound heparin hydrogel had no effect on the drop in the number of platelets induced by PVA hydrogel, but increased the fractional rate of platelet destruction from approximately 0.35/d to an average value of 0.42/d.

Animals↗