Protein adsorption on polyurethane catheters modified with a novel antithrombin‐heparin covalent complex

Abstract

Highly anticoagulant covalent antithrombin-heparin complex (ATH) was covalently grafted onto polyurethane catheters to suppress adsorption/activation of procoagulant proteins and enhance adsorption/activation of anticoagulant proteins for blood compatibility. Consistency of catheter coating was demonstrated using immunohistochemical visualization of ATH. The ability of the resulting immobilized ATH heparin chains to bind antithrombin (AT) from plasma, as measured by binding of 125 I-radiolabeled AT, was greater than that for commercially-available heparin-coated catheters, and much greater than for uncoated catheters. Complementary measurements of antifactor Xa (FXa) activity and plasma protein binding were also performed. Both ATH-coated and heparin-coated catheters demonstrated functional binding of exogenous AT. However, the ATH-coated catheters gave a trend towards elevated antiFXa activities/AT binding ratios, consistent with the higher active pentasaccharide content in starting ATH. Western blot analysis of proteins adsorbed to catheters after incubation with rabbit plasma established protein binding profiles that showed AT and albumin as major plasma proteins adsorbed to ATH-coated catheters, while AT and altered forms of fibrinogen were major plasma protein species adsorbed to heparinized catheters.

Acylase‐containing polyurethane coatings with anti‐biofilm activity

“…Polyurethanes, in particular, are attractive supports due to their rapid and simple preparation and tunable properties that, when used as scaffolds, yield stable bioplastics (Drevon et al, 2001(Drevon et al, , 2002Gill and Ballesteros, 2000;Gordon et al, 1999;LeJeune et al, 1997LeJeune et al, , 1999Vasudevan et al, 2004). Additionally, as polymers and coatings for implantable materials and medical devices, including catheters and metal stents, polyurethanes are widely used in tissue engineering and regenerative medicine (Du et al, 2007;Guelcher, 2008;Klement et al, 2006;Santerre et al, 2005;Trigwell et al, 2006). Bakker et al (2000) have previously shown that acylase could be immobilized in polyurethane foams while retaining activity, although such foams are impractical for use as coatings on catheter surfaces.…”

Corn trypsin inhibitor coating attenuates the prothrombotic properties of catheters in vitro and in vivo

“…The open ends of the PCI catheters were sealed with implant-grade silicone adhesive (Rhodia, Ventura, CA). Using the procedure of Du et al [29], a base coat was first applied by immersing the catheter segments in a 10 ml solution of glycidyl methacrylate containing 0.1 g AIBN for 20 min at 23°C. After removing the catheters, excess solution was blotted with filter paper and the catheters were incubated at 80°C for 40 min followed by an annealing step at 50°C for 20 min.…”

Plasma Protein Adsorption and Platelet Adhesion on Heparin-Immobilized Polyurethane Films

“…The anticoagulant activity of the heparinized surfaces depends on the ability of immobilized heparin to bind to AT. It is reported that heparinized surfaces can have variable anticoagulant activity, and negatively charged long heparin chains may also promote protein binding and platelet aggregation [8,9].…”