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

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, we propose a novel modulatory coating system based on C1‐esterase inhibitor (C1INH) functionalized polymer brushes, which effectively regulates the activation of FXII. We demonstrated using SPR 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, we showed 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.This article is protected by copyright. All rights reserved

Mass‐Spectrometric Identification of Proteins and Pathways Responsible for Fouling on Poly(ethylene glycol) Methacrylate Polymer Brushes

“…Modern strategies to prevent unwanted fouling, coagulation, and bacterial adhesion often combine active functions with polymer‐based coatings that prevent non‐specific protein adsorption from the biological environment. [ 5–10 ] In this regard, polymer brushes have emerged as a promising strategy to combat protein fouling. They are comprised of end‐tethered polymer chains on surfaces, which can resist non‐specific protein adsorption due to their unique structural, chemical, and even topological properties.…”