Haraguchi Kazutoshi, Takehisa Toru, Mizuno Toshihide, Kubota Kazuomi
Material Chemistry Laboratory, Kawamura Institute of Chemical Research, Sakura, Chiba 285-0078 Japan.
Department of Applied Molecular Chemistry, College of Industrial Technology, Nihon University, Narashino, Chiba 275-8575 Japan.
ACS Biomater Sci Eng. 2015 Jun 8;1(6):352-362. doi: 10.1021/acsbiomaterials.5b00079. Epub 2015 May 22.
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(,-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) 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) 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.
抗血栓形成性是生物医学设备所用材料所需的最关键特性之一，尤其是在与血液接触的设备中。使用血浆蛋白和全血，针对蛋白质吸附、血栓形成、血小板活化和凝血动力学，研究了由疏水性聚（丙烯酸2 - 甲氧基乙酯）（M）和亲水性聚（N，N - 二甲基丙烯酰胺）（D）链段组成的两亲性嵌段共聚物涂层表面的抗血栓形成性。在高产率和高分子量条件下，采用一锅法可逆加成 - 断裂链转移（RAFT）聚合反应合成了三种类型的嵌段共聚物和一种无规共聚物。分别具有MDM和（MD）结构的三嵌段和四臂嵌段共聚物对包括聚氯乙烯（PVC）管在内的有机和无机基材均表现出良好的附着力，与二嵌段或无规共聚物涂层以及未涂层对照相比，所得涂层表面表现出优异的蛋白质排斥性和血液相容性。在全血的钱德勒环路法中，涂覆有MDM和（MD）的PVC管对血液衍生蛋白表现出改善的抗血栓性和吸附抗性。通过血栓弹力图（内在和外在凝血途径中血液凝固行为的抑制）和血小板功能分析（两种刺激下血小板聚集活性的显著降低），用人全血也证实了这种高血液相容性。基于MDM涂层表面的结构分析对抗血栓形成性进行了讨论。本研究结果将通过使用简单且环保的方法，推动开发具有优异抗血栓形成特性的更有效的生物医学和分析设备。
