Heparin bioconjugate with a thermoresponsive cationic branched polymer: a novel aqueous antithrombogenic coating material.
Heparin bioconjugate with a thermoresponsive cationic branched polymer: a novel aqueous antithrombogenic coating material.
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DOI：
10.1021/la700323m
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发表时间：
2007-06
期刊：
影响因子：
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通讯作者：
Y. Nakayama;Ryohei Okahashi;R. Iwai;K. Uchida
中科院分区：
文献类型：
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作者：
Y. Nakayama;Ryohei Okahashi;R. Iwai;K. Uchida
为了降低人工血液接触装置和天然组织的血栓形成潜力，我们开发了一种新型的水性抗血栓形成涂层材料，其包含肝素生物缀合物，该肝素生物缀合物包含作为表面活性剂的温敏阳离子聚合物。以N-[3-（二甲氨基）丙基]丙烯酰胺为引发剂-转移剂-终止剂（iniferter）进行活性自由基光聚合，再以四（N，N-二乙基二硫代氨甲酰基甲基）苯为引发剂进行N-异丙基丙烯酰胺的聚合，得到了一种多功能iniferter聚合物。所获得的聚合物具有四个支链，每个支链由阳离子PDMAPAAm嵌段（Mn：约100）组成。3000 g.mol（-1））形成肝素结合的内部结构域和热响应性PNIPAM嵌段（Mn：约3000 g. 6000 g.mol（-1））形成用于表面固定的外部结构域;在水介质中简单混合后立即发生聚合物与肝素的生物缀合。因为肝素生物缀合物的较低临界溶液温度为约35 ℃，所以其可以在室温下从水溶液涂覆。通过润湿性测量和表面化学成分分析，在几种常用的聚合物上，以及通过肝素染色在胶原蛋白片和大鼠皮肤组织上，证明了涂层在37 ℃以下具有优异的吸附性和高耐久性。在肝素生物缀合物涂覆的表面上显著防止血液凝固。因此，开发的温度响应性生物缀合物似乎满足生物相容性水性涂层材料的初始要求。
With a view to reducing the thrombogenic potential of artificial blood-contact devices and natural tissues, we developed a novel aqueous antithrombogenic coating material, comprising a heparin bioconjugate that incorporated a thermoresponsive cationic polymer as a surfactant. The polymer was prepared by the sequential steps of initiator-transfer agent-terminator (iniferter)-based living radical photopolymerization of N-[3-(dimethylamino)propyl]acrylamide, followed by the polymerization of N-isopropylacrylamide from tetra(N,N-diethyldithiocarbamylmethyl)benzene as a multifunctional iniferter. The polymer obtained possessed four branched chains, each consisting of a cationic PDMAPAAm block (Mn: ca. 3000 g.mol(-1)) forming an inner domain for heparin binding and a thermoresponsive PNIPAM block (Mn: ca. 6000 g.mol(-1)) forming an outer domain for surface fixation; bioconjugation of the polymer with heparin occurred immediately upon simple mixing in an aqueous medium. Because the lower critical solution temperature of the heparin bioconjugate was approximately 35 degrees C, it could be coated from an aqueous solution at room temperature. The excellent adsorptivity and high durability of the coating below 37 degrees C was demonstrated on several generally used polymers by wettability measurement and surface chemical compositional analysis, and on collagen sheets and rat skin tissue by heparin staining. Blood coagulation was significantly prevented on the heparin bioconjugate-coated surfaces. The thermoresponsive bioconjugate developed therefore appeared to satisfy the initial requirements for a biocompatible aqueous coating material.