Authors Salchert, K. ; Gouzy, M.-F. ; Glorius, M. ; Kühn, A. ; Nitschke, M. ; Werner, C.
Title Immobilization of an anticoagulant benzamidine derivative: Effect of spacer arms and carrier hydrophobicity on thrombin binding
Date 22.07.2005
Number 12809
Abstract Prevention of blood coagulation is very often a prerequisite for successful medical devices. For that purpose, passivation of the key coagulation enzyme thrombin through the derivatization of the material’s surface with an amidine-based molecule has been found to be promising. To further enhance the efficiency of this approach, thin layers of maleic anhydride copolymers offering different physico-chemical characteristics were tethered with carboxyl terminated polyethylene glycol to covalently immobilize a benzamidine-type derivative. The free carboxyl surface groups produced by the attachment of polyethylene glycol (PEG) were quantified by Ag+ labeling and subsequent XPS detection. The film thickness as well as the carboxyl group content were found to be clearly dependent on the copolymer hydrophobicity and the nature of the PEG molecule. For the assessment of the anchorage of the thrombin to the benzamidine-derivative functionalized surfaces, the substrates were immersed in a buffered thrombin solution and the enzyme adsorption was studied using immunostaining/confocal laser scanning microscopy. Higher degrees of thrombin binding were observed for substrates configured with the hydrophilic compared to the more hydrophobic copolymer. Moreover, surface-bound spacers based on a, ·-heterobifunctional PEG amino acids (aAm, ·Ac-PEG) also enhanced the benzamidine surface density in comparison to homofunctional PEG diacids (aAc, ·Ac-PEG) because of a lower degree of carboxyl inactivation due to PEG ‘bridging’. Altogether, the choice of copolymer coatings and the type of PEG spacers were demonstrated to enhance the efficiency of the thrombin scavenging by the covalently immobilized coagulation inhibitor.
Publisher Acta Biomaterialia
Citation Acta Biomaterialia 1 (2005) 441-449

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