Antithrombogenic Properties of Amphiphilic Block Copolymer Coatings: Evaluation of Hemocompatibility Using Whole Blood.

Antithrombogenicity is one of the most critical properties required for materials used in biomedical devices, particularly in devices that contact blood. The antithrombogenicity of surfaces coated with amphiphilic block copolymers composed of hydrophobic poly(2-methoxyethyl acrylate) (M) and hydrophilic poly(N,N-dimethylacrylamide) (D) segments was investigated using plasma protein and whole blood with regard to protein adsorption, thrombus formation, platelet activation, and clotting kinetics. Three types of block copolymers and a random copolymer were synthesized using one-pot reversible addition-fragmentation chain-transfer (RAFT) polymerization under conditions of high yield and high molecular weight. Triblock and 4-arm block copolymers with MDM and (MD)4 architecture, respectively, showed good adhesion to both organic and inorganic substrates, including polyvinyl chloride (PVC) tubes, and the resulting coated surfaces showed superior protein repellency and hemocompatibility compared to the diblock or random copolymer coatings and noncoated control. In a Chandler-loop method with whole blood, PVC tubes coated with MDM and (MD)4 showed improved thromboresistance and adsorption resistance to blood-derived proteins. This high hemocompatibility was also confirmed with human whole blood by thrombelastography (suppression of blood-clotting behavior in both intrinsic and extrinsic coagulation pathways) and platelet function analyses (significant reductions in the aggregation activity of platelets under two types of stimulation). The antithrombogenicity has been discussed based on the structural analyses of the MDM-coated surface. The results of this study will enable the development of more effective biomedical and analytical devices with excellent antithrombogenic characteristics by using a simple and environmentally friendly approach.

Highly protein-resistant coatings and suspension cell culture thereon from amphiphilic block copolymers prepared by RAFT polymerization.

Novel amphiphilic block copolymers composed of hydrophobic (poly(2-methoxyethyl acrylate): M) and hydrophilic (poly(N,N-dimethylacrylamide): D) segments were synthesized by living radical polymerization: a reversible addition-fragmentation chain-transfer polymerization. Two types of amphiphilic block copolymers, triblock (MDM) and 4-arm block ((MD)4) copolymers with specific compositions (D/M = (750-1500)/250), were prepared by a versatile one-pot synthesis. These copolymers show good adhesion to various types of substrates (e.g., polystyrene, polycarbonate, polypropylene, Ti, and glass), and the surface coating showed high protein repellency and a low contact angle for water, regardless of the substrate. The two opposing characteristics of high protein repellency and good substrate adhesion were achieved by the combined effects of the molecular architecture of the block copolymers, the high molecular weight, and the characteristics of each segment, that is, low protein adsorption capability of both segments and low glass transition temperature of the hydrophobic segment. Further, a polystyrene dish coated with the MDM block copolymer could be sterilized by γ-ray irradiation and used as a good substrate for a suspension cell culture that exhibits low cell adhesion and good cell growth.

The Proton Cryptate of Hexaethylenetetramine.

The next higher homologue of hexamethylenetetramine was synthesized as the proton cryptate H+ @1⋅Br- (shown schematically), and its X-ray structure determined. The proton trapped by the lone pairs accumulated at the center of the T-symmetric tetraaza cage could not be exchanged or removed, even after heating for three days in 3 M NaOD.