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Antithrombogenic Properties of Amphiphilic Block Copolymer Coatings: Evaluation of Hemocompatibility Using Whole
Kazutoshi Haraguchi1,2, Toru Takehisa1,3, Toshihide Mizuno4
1Material Chemistry Laboratory, Kawamura Institute of Chemical Research, Sakura, Chiba 285-0078 Japan.
Abstract:
Antithrombogenicity is one of the most critical properties required for materials used in biomedical devices, particularly in devices that contact blood. The antithrombogenicity of surfaces coated with amphiphilic block copolymers composed of hydrophobic poly(2-methoxyethyl acrylate) (M) and hydrophilic poly(N,N-dimethylacrylamide) (D) segments was investigated using plasma protein and whole blood with regard to protein adsorption, thrombus formation, platelet activation, and clotting kinetics. Three types of block copolymers and a random copolymer were synthesized using one-pot reversible addition-fragmentation chain-transfer (RAFT) polymerization under conditions of high yield and high molecular weight. Triblock and 4-arm block copolymers with MDM and (MD)4 architecture, respectively, showed good adhesion to both organic and inorganic substrates, including polyvinyl chloride (PVC) tubes, and the resulting coated surfaces showed superior protein repellency and hemocompatibility compared to the diblock or random copolymer coatings and noncoated control. In a Chandler-loop method with whole blood, PVC tubes coated with MDM and (MD)4 showed improved thromboresistance and adsorption resistance to blood-derived proteins. This high hemocompatibility was also confirmed with human whole blood by thrombelastography (suppression of blood-clotting behavior in both intrinsic and extrinsic coagulation pathways) and platelet function analyses (significant reductions in the aggregation activity of platelets under two types of stimulation). The antithrombogenicity has been discussed based on the structural analyses of the MDM-coated surface. The results of this study will enable the development of more effective biomedical and analytical devices with excellent antithrombogenic characteristics by using a simple and environmentally friendly approach.
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