Thermoresponsive Heparin Bioconjugate as Novel Aqueous Antithrombogenic Coating Material

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• 作者：Yasuhide Nakayama ; Saori Yamaoka ; Yasushi Nemoto ; Borovkov Alexey ; Kingo Uchida
• 刊名：Bioconjugate Chemistry
• 出版年：2011
• 出版时间：February 16, 2011
• 年：2011
• 卷：22
• 期：2
• 页码：193-199
• 全文大小：798K
• 年卷期：v.22,no.2(February 16, 2011)
• ISSN：1520-4812

文摘

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 with M_n of 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 掳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 掳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 掳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.