Thermoresponsive heparin bioconjugate as novel aqueous antithrombogenic coating material.
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 °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.
Division of Medical Engineering and Materials, National Cerebral and Cardiovascular Center Research Institute, Osaka 565-8565, Japan. nakayama@ri.ncvc.go.jp
Yasuhide
Y
Nakayama
Saori
S
Yamaoka
Yasushi
Y
Nemoto
Borovkov
B
Alexey
Kingo
K
Uchida
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006493:Heparin / Q000737:chemistry*; D008422:Materials Testing; D008689:Methacrylates / Q000737:chemistry*; D015394:Molecular Structure; D009757:Nylons / Q000737:chemistry*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013499:Surface Properties; D013696:Temperature; D014867:Water / Q000737:chemistry
D020099:Coated Materials, Biocompatible; D008689:Methacrylates; D009757:Nylons; D010975:Platelet Aggregation Inhibitors; C407037:poly(2-(dimethylamino)ethyl methacrylate); D014867:Water; D006493:Heparin