Antithrombotic coating with sheltered positive charges prevents contact activation by controlling Factor XII-biointerface binding

The development of an antithrombotic surface that prevents coagulation activation without interfering with hemostasis is the “holy grail” for blood-contacting devices. Such an advance would restrain device-induced thrombogenesis, and decrease the need for anticoagulant use in conjunction with devices, which would in turn reduce the bleeding risk. Herein, by optimizing factor (F)XII-surface binding rather than preventing its surface adsorption, we developed a substrate-independent antithrombotic coating with sheltered positive charges, the function of which was verified in vitro in human blood and using a carotid artery-jugular vein shunt model in rabbits. The new coating exhibits a strong interaction with FXII but results in a low reciprocal activation of the contact pathway. These findings contradict the prevailing strategy of designing antithrombotic materials through protein-repelling surfaces. Besides providing a universal coating which can benefit most blood-contacting devices, this work also pioneers a simple, but powerful and counterintuitive, guideline for designing antithrombotic surfaces.