Blood-compatible biomaterials by surface coating with a novel antithrombin–heparin covalent complex

• Published in: Biomaterials 2002, Vol.23 (2), p.527-535
• Main Authors: Klement, P, Du, Y.J, Berry, L, Andrew, M, Chan, A.K.C
• Format: Article
• Language: English
• Subjects: Animals; Anticoagulant; Antithrombin; Antithrombins - chemistry; ATH; Biocompatible Materials; Blood; Heparin; Heparin - chemistry; Male; Polycarbonate urethane; Rabbits; Surface grafting; Surface Properties
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/S0142-9612(01)00135-1

Covalent antithrombin–heparin complex (ATH) was covalently grafted to a polycarbonate urethane (Corethane ®) endoluminal graft (a kind gift of Corvita Corporation) after being activated using 0.3% m/m NaOCl in 0.15 m phosphate pH 6.0. ATH graft density (1.98×10 −7 mol/m 2) was 6 times the maximum amount of unfractionated heparin (UFH) that could be bound to polycarbonate urethane surfaces. Surface-bound ATH could be stored in sterile 0.15 m NaCl at 4°C for at least 2 months with good antithrombotic activity before being implanted into rabbits. Analysis of ATH-coated tubing showed that it contained significant direct thrombin inhibitory activity. In vivo testing in a rabbit model was compared to non-activated non-coated surfaces, activated-non-coated surfaces, hirudin-coated surfaces and antithrombin (AT)-coated surfaces. The weight of the clot generated in the ATH-coated graft tubing was significantly less than the weight of the clot generated within the hirudin-coated graft ( p=0.03 with a 1-tailed Student's t test). The anticoagulant nature of ATH grafts in vivo was shown to be due to bound ATH because both the AT-coated surfaces and non-coated but activated surfaces showed similar thromboresistant efficacy to that of untreated material (ANOVA; p