Argatroban- and copper-modified polymers with improved thromboresistance and antimicrobial properties

Abstract

AbstractThis paper describes a novel approach the development of biocompatible polyvinyl chloride (PVC) and polyurethane (PU) polymers, modified with copper (II) ions followed by the immobilisation the thrombin inhibitor argatroban (AG) using dopamine chemistry. The surface loading of the immobilised AG was 6.06 µg cm−2 on PVC and 6.66 µg cm−2 on PU, confirmed by FTIR and inhibitor concentration measurements. Both AG/Cu-modified polymers produced NO by catalytically decomposing S-nitrosothiol, reaching NO levels in plasma of 0.59 × 10–10$$\text{mol} \, {\text{cm}}^{-2} \, {\text{min}}^{-1}$$ mol cm - 2 min - 1 for AG/Cu-PVC and 0.51 × 10–10$$\text{mol} \, {\text{cm}}^{-2} \, {\text{min}}^{-1}$$ mol cm - 2 min - 1 for AG/Cu-PU, matching endothelial cell-produced physiological levels. This modification improved the haemocompatibility of the polymers through thrombin inhibition and reduced platelet aggregation and adhesion. Additionally, both modified polymers inhibited Staphylococcus aureus adhesion, growth and viability, confirming their acquired antibacterial properties. Antibacterial activity against Escherichia coli was also observed. These results demonstrate that modifying PVC and PU surfaces with copper (II) and AG produced materials with dual antithrombotic and antibacterial functions. Graphical abstract