Thermoresponsive Heparin Bioconjugate as Novel Aqueous Antithrombogenic Coating Material
Thermoresponsive Heparin Bioconjugate as Novel Aqueous Antithrombogenic Coating Material
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作为新型水性抗血栓形成涂层材料的热响应性肝素生物共轭物
DOI：
10.1021/bc100267z
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发表时间：
2011
影响因子：
4.7
通讯作者：
K.Uchida
中科院分区：
文献类型：
--
作者：
Y.Nakayama;S.Yamaoka;Y.Nemoto;B.Alexey;K.Uchida
为了降低心血管装置中血液接触材料如合成聚合物或组织工程组织的血栓形成潜力，开发了一种新型热响应性水性抗血栓涂层材料，该材料包括肝素生物结合物和六支星形聚(2-(二甲氨基乙基)甲基丙烯酸酯)(6B-PDMAEMA)，具有温度响应性和阳离子特性。以六(N，N-二乙基二硫代氨基甲基甲基)苯为原料，通过引发剂-转移剂-终止剂(Iniferter)活性自由基光聚合，设计了一种锰含量约为24 kDa的6B-PDMAEMA的原型化合物。当肝素和6B-PDMAEMA水溶液简单混合形成颗粒时，肝素与6B-PDMAEMA的生物偶联就发生了。在肝素/6B-PDMAEMA混合重量比大于2.5的情况下，在25℃时，粒径小于几百纳米。由于阻止了6B-PDMAEMA的生物偶联形式的水解，所以颗粒非常稳定。由于生物结合物形成微粒的较低临界溶液温度约为20至36°C，因此涂层可以在较低温度下的水溶液中完成。表面化学成分分析表明，该涂层在37℃以上对有机硅和聚乙烯薄膜具有良好的吸附性能和较高的耐久性。生物偶联涂层表面的凝血功能显著降低。因此，这里开发的热响应性生物偶联物似乎满足了生物相容水性涂层材料的初始要求。
A novel thermoresponsive aqueous antithrombogenic coating material comprising a heparin bioconjugate with a six-branched, star-shaped poly(2-(dimethylaminoethyl)methacrylate) (6B-PDMAEMA), which has both thermoresponsive and cationic characters, was developed to reduce the thrombogenic potential of blood-contacting materials such as synthetic polymers or tissue-engineered tissues in cardiovascular devices. 6B-PDMAEMA withMnof ca. 24 kDa was designed as a prototype compound by initiator-transfer agent-terminator (iniferter)-based living radical photopolymerization from hexakis(N,N-diethyldithiocarbamylmethyl)benzene. Bioconjugation of heparin with 6B-PDMAEMA occurred as soon as both aqueous solutions were simply mixed to form particles. The particle size at 25 °C was less than several hundred nanometers in diameter under a heparin/6B-PDMAEMA mixing weight ratio of over 2.5. The particles were very stable because of the prevention of hydrolysis of 6B-PDMAEMA in its bioconjugated form. Because the lower critical solution temperature of the bioconjugate ranges from approximately 20 to 36 °C for the formation of microparticles, the coating could be done in an aqueous solution at low temperatures. The excellent adsorptivity and high durability of the coating above 37 °C was demonstrated on silicone and polyethylene films by surface chemical compositional analysis. Blood coagulation was significantly reduced on the bioconjugate-coated surfaces. Therefore, the thermoresponsive bioconjugate developed here appears to satisfy the initial requirements for a biocompatible aqueous coating material.