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

Abstract

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)

Biocompatible micellar nanovectors achieve efficient gene transfer to vascular lesions without cytotoxicity and thrombus formation

“…[25][26][27] There are previous reports that the surface modification of biomaterials with PEG appreciably reduces thrombogenicity. 25,[28][29][30][31][32] Thus, it is widely accepted that PEG shields the cationic surface of biomaterials, reducing their thrombogenicity. 31 In this study, the PEG-b-P[Asp(DET)] micelle system showed no agglomeration even in the presence of blood components including serum albumin (Table 1 and Figure 4), platelets ( Figure 5) and erythrocytes ( Figure 6), whereas BPEI and P[Asp(DET)] polyplexes definitely showed the aggregate formation due to their positively charged character under the same conditions.…”

Dynamic wettability study on the functionalized PEGylated layer on a polylactide surface constructed by the coating of aldehyde–ended poly(ethylene glycol) (PEG)/polylactide (PLA) block copolymer

“…Particularly, poly(ethylene glycol) (PEG) coating is the most common way to minimize nonspecific fouling of a material surface with biocomponents [4,5], including plasma proteins, and has been performed by a wide variety of methods [6][7][8][9][10][11]. However, most of the PEG-coated surfaces so far reported possess no reactive group on the PEG chain end.…”

Measurements of attractive forces between proteins and end-grafted poly(ethylene glycol) chains

“…Its prevalent use is due largely to its low toxicity and low immunogenicity (1). In addition, due to its protein resistance, it is widely used as a stabilizing surface coating in biological environments (3)(4)(5)(6)(7). For example, PEG-functionalization of liposomes increased their blood circulation times by nearly an order of magnitude (4).…”

“…For example, PEG-functionalization of liposomes increased their blood circulation times by nearly an order of magnitude (4). In the clinic, ethylene oxide surface grafts are used to reduce protein adsorption onto the surfaces of biomedical polymers (1)(2)(3)(5)(6)(7). This is important for controlling the biological responses to the latter, in part, because protein adsorption is a well established first step in the humoral response against foreign materials (2,8,9).…”