title: Heparin bioconjugate with a thermoresponsive cationic branched polymer: a novel aqueous antithrombogenic coating material.
abstract: 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.
authors.affiliation: Department of Bioengineering, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, Hokkaido University, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. nakayama@ri.ncvc.go.jp
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Ryohei
authors.initials: R
authors.lastname: Okahashi
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Iwai
authors.forename: Kingo
authors.initials: K
authors.lastname: Uchida
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis* / Q000737:chemistry; D003094:Collagen / Q000737:chemistry; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D006493:Heparin / Q000737:chemistry*; D006358:Hot Temperature; D008422:Materials Testing; D051381:Rats; D012867:Skin / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D013501:Surface-Active Agents / Q000737:chemistry*; D017155:Wettability
chemical_list: D000180:Acrylic Resins; D020099:Coated Materials, Biocompatible; D005343:Fibrinolytic Agents; D013501:Surface-Active Agents; C052970:poly-N-isopropylacrylamide; D006493:Heparin; D003094:Collagen