PB0590 - The control of protein binding on bio-interface by a novel coating to prevent contact activation on biomaterials

Background: The coagulation system activates quickly to "protect" the body when most biomaterials come in contact. To prevent thrombotic risk, thus administration of anticoagulants is necessary but it comes with the bleeding risk. So, research efforts are focused intensely on endowing the material with anti-thrombogenic properties. A consensus has been reached that bio-interface-induced contact activation (BCA) is the principal pathway for thrombogenesis induced by biomaterials. It is known that positively charged surfaces interact strongly with FXII and can inhibit BCA but such surfaces show poor hemocompatibility.

Aims: Our objective is to develop a protected positively charged coating with high hemocompatibility while maintaining strong interactions with FXII to develop anti-thrombogenic blood contacting surfaces for practical applications and study the mechanism of function of the coating.

Methods: In vitro contact activation, and thrombin generation assays are used to verify the function of the coating on control surfaces in human plasma. The hemocompatibility of the coating is verified by coagulation assays, measurement of protein corona by proteomics, and immune activation analyses. An arteriovenous shunt model in rabbits is developed to demonstrate the potential of the new coatings.

Results: The coating developed can be conferred on any substrate to inhibit contact activation and thrombin generation (Image. 1). The coating does not affect the hemostatic balance of the blood and shows excellent hemocompatibility. The coating inhibits material-induced coagulation activation in animals without anticoagulation (Image. 2).

Conclusion(s): The coating can be applied to diverse substrates without the need of pre-treatment. The stabilizes FXII on the surface and prevents contact activation thereby preventing thrombogenesis without bleeding risk. Besides providing a universal coating for inhibiting contact activation on commercial blood-contact biomaterials, the work also established the concept of controlling the protein behavior on the bio-interface to endow them with superior hemocompatibility.