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

• Published in: Macromolecular bioscience Vol. 24; no. 2; pp. e2300321 - n/a
• Main Authors: Witzdam, Lena, Vosberg, Berlind, Große‐Berkenbusch, Katharina, Stoppelkamp, Sandra, Wendel, Hans Peter, Rodriguez‐Emmenegger, Cesar
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.02.2024
• Subjects: Antifouling substances; Blood; Blood Coagulation; Blood plasma; Brushes; C1‐esterase‐inhibitor; Cascade chemical reactions; Clotting; Coagulation; Coagulation factors; Coating; Coatings; Factor XII - metabolism; Factor XII - pharmacology; Factor XIIa - metabolism; FXII activation; hemocompatibility; hemocompatible surface modification; Hemostasis; Hemostatics; Medical devices; Medical equipment; Plasma kallikrein; Plasma proteins; polymer brushes; Polymers; Polymers - pharmacology; Proenzymes; Protective coatings; Surface plasmon resonance; β‐FXIIa; β-FXIIa; C1-esterase-inhibitor; hemocompatibility; hemocompatible surface modification; FXII activation; polymer brushes
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.202300321

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. The hemocompatible nanocoating is composed of antifouling polymer brushes (passive level) that are functionalized with C1‐esterase inhibitor (modulatory level) that inhibits the autocatalytic amplification mechanism of factor XII activation. The synergistic interplay between the passive and modulatory levels of the coating allows the prevention of surface‐induced coagulation and clot formation.