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2024_Macromolecular_Tackling_WitzdamL.pdf (2.51 MB)

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2023-09-24

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cc by (c) Witzdam, Lena et al., 2023
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/208657

Tackling the Root Cause of Surface-Induced Coagulation: Inhibition of FXII Activation to Mitigate Coagulation Propagation and Prevent Clotting

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https://doi.org/10.1002/mabi.202300321

Abstract

Factor XII (FXII) is a zymogen present in blood that tends to adsorb onto the surfaces of blood-contacting medical devices. Once adsorbed, it becomes activated, initiating a cascade of enzymatic reactions that lead to surface-induced coagulation. This process is characterized by multiple redundancies, making it extremely challenging to prevent clot formation and preserve the properties of the surface. In this study, a novel modulatory coating system based on C1-esterase inhibitor (C1INH) functionalized polymer brushes, which effectively regulates the activation of FXII is proposed. Using surface plasmon resonance it is demonstrated that this coating system effectively repels blood plasma proteins, including FXII, while exhibiting high activity against activated FXII and plasma kallikrein under physiological conditions. This unique property enables the modulation of FXII activation without interfering with the overall hemostasis process. Furthermore, through dynamic Chandler loop studies, it is shown that this coating significantly improves the hemocompatibility of polymeric surfaces commonly used in medical devices. By addressing the root cause of contact activation, the synergistic interplay between the antifouling polymer brushes and the modulatory C1INH is expected to lay the foundation to enhance the hemocompatibility of medical device surfaces.© 2023 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.

Subject

Coagulació sanguínia, Polímers

Subject (English)

Blood Coagulation, Polymers

Citation

Witzdam L;Vosberg B;Große-Berkenbusch K;Stoppelkamp S;Wendel HP;Rodriguez-Emmenegger C. Tackling the Root Cause of Surface-Induced Coagulation: Inhibition of FXII Activation to Mitigate Coagulation Propagation and Prevent Clotting. Macromolecular Bioscience, 2024, 24, 2, e2300321-NA

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Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))

Citation

WITZDAM, L., et al. Tackling the Root Cause of Surface-Induced Coagulation: Inhibition of FXII Activation to Mitigate Coagulation Propagation and Prevent Clotting. Macromolecular Bioscience. 2024. Vol. 24, num. 2, pags. e2300321. ISSN 1616-5195. [consulted: 9 of August of 2026]. Available at: https://hdl.handle.net/2445/208657

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