A Novel C1-Esterase Inhibitor Oxygenator Coating Prevents FXII Activation in Human Blood.

Biomolecules
Katharina GerlingSandra Stoppelkamp

Abstract

The limited hemocompatibility of currently used oxygenator membranes prevents long-term use of artificial lungs in patients with lung failure. To improve hemocompatibility, we developed a novel covalent C1-esterase inhibitor (C1-INH) coating. Besides complement inhibition, C1-INH also prevents FXII activation, a very early event of contact phase activation at the crossroads of coagulation and inflammation. Covalently coated heparin, as the current anticoagulation gold standard, served as control. Additionally, a combination of both coatings (C1-INH/heparin) was established. The coatings were tested for their hemocompatibility by dynamic incubation with freshly drawn human whole blood. The analysis of various blood and plasma parameters revealed that C1-INH-containing coatings were able to markedly reduce FXIIa activity compared to heparin coating. Combined C1-INH/heparin coatings yielded similarly low levels of thrombin-antithrombin III complex formation as heparin coating. In particular, adhesion of monocytes and platelets as well as the diminished formation of fibrin networks were observed for combined coatings. We could show for the first time that a covalent coating with complement inhibitor C1-INH was able to ameliorate he...Continue Reading

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Citations

Aug 27, 2021·ACS Biomaterials Science & Engineering·Meili ZhangJohn F Fraser

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA
ELISAs
fluorescence microscopy
fluorescence
scanning electron microscopy

Software Mentioned

GraphPad
ImageJ
GraphPad Prism

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