title: Creation of a blood-compatible surface: a novel strategy for suppressing blood activation and coagulation using a nitroxide radical-containing polymer with reactive oxygen species scavenging activity.
abstract: Various polymeric materials have been used in medical devices, including blood-contacting artificial organs. Contact between blood and foreign materials causes blood cell activation and adhesion, followed by blood coagulation. Concurrently, the activated blood cells release inflammatory cytokines together with reactive oxygen species (ROS). We have hypothesized that the suppression of ROS generation plays a crucial role in blood activation and coagulation. To confirm this hypothesis, surface-coated polymers containing nitroxide radical compounds (nitroxide radical-containing polymers (NRP)) were designed and developed. The NRP was composed of a hydrophobic poly(chloromethylstyrene) (PCMS) chain to which 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) moieties were conjugated via condensation reaction of the chloromethyl groups in PCMS with the sodium alcoholate group of 4-hydroxy-TEMPO. Blood compatibility was investigated by placing NRP-coated beads in contact with rat whole blood. The amount of ROS generated on PCMS-coated beads used as a control increased significantly with time, while NRP-coated beads suppressed ROS generation. It is interesting to note that the suppression of inflammatory cytokine generation by NRP-coated beads was shown to be significantly higher than that by PCMS-coated beads. Both platelet and leukocyte adhesion to the beads were suppressed with increasing TEMPO incorporation in the polymer. These results confirm that the suppression of ROS by NRP prevents inflammatory cytokine generation, which in turn results in the suppression of blood activation and coagulation on the beads.
authors.affiliation: Department of Materials Sciences, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshitomi
authors.forename: Yu
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nagasaki
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000737:chemistry / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D008297:Male; D008422:Materials Testing / Q000379:methods; D011137:Polystyrenes / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D020099:Coated Materials, Biocompatible; D003497:Cyclic N-Oxides; D016207:Cytokines; D011137:Polystyrenes; D017382:Reactive Oxygen Species; C426943:poly(p-chloromethylstyrene); C003959:TEMPO