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Covalently immobilized thrombomodulin inhibits coagulation and complement activation of artificial surfaces in vitro

Paper ID Volume ID Publish Year Pages File Format Full-Text
12848 819 2004 13 PDF Available
Title
Covalently immobilized thrombomodulin inhibits coagulation and complement activation of artificial surfaces in vitro
Abstract

Thrombomodulin (TM) serves as the endothelial cell receptor for thrombin and alters its characteristics from pro- to anticoagulant. Additionally, it promotes the formation of activated protein C. We evaluated the conservation of the overall outcome of these functions in recombinant TM linked to artificial surfaces by incubation with human whole blood in vitro.TM was covalently immobilized through poly(ethylene glycol) (PEG) spacers onto thin films of poly(octadecene alt maleic anhydride) covering planar glass substrates. TM binding to the polymer films was achieved after active ester formation at the carboxylic acid terminus of the PEG spacers and thoroughly characterized by HPLC-based amino acid analysis, immunofluorescence and ellipsometry. TM-coated samples were incubated for 3 h with freshly drawn whole human blood anticoagulated with heparin (5 IU/ml) using in-house developed incubation systems. The substantially reduced activation of blood coagulation (TAT) for TM-coated samples correlates well with the degree of contact activation (bradykinin and FXIIa formation) while no significant effects were observed for the platelet activation (PF4). Further, complement activation (C5a levels), was strongly diminished at the TM-containing surfaces. We conclude that the suggested method for preparation of TM immobilization may serve to prepare model substrates for studies on TM interactions but similarly provides a promising coating strategy for blood contacting medical devices.

Keywords
Anticoagulant; Complement; Hemocompatibility; In vitro test; Platelet activation; Thrombomodulin
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Covalently immobilized thrombomodulin inhibits coagulation and complement activation of artificial surfaces in vitro
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 25, Issue 21, September 2004, Pages 5101–5113
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us