Development of substrate-independent heparin coating to mitigate surface-induced thrombogenesis: efficacy and mechanism

Abstract

Heparin coatings are widely applied on blood-contact materials to reduce the use of anticoagulants during blood treatment. However, the previous heparin coatings formed via covalent binding or electrostatic bonding commonly require complex surface premodification, and the blood coagulation pathway was significantly inhibited to potentially increase the bleeding risk. This contradicts the intended purpose and deviates from the anticoagulation mechanism of the heparin coatings. Herein, we present a facile and substrate-independent coating, achieved through the co-deposition of dopamine/chitosan followed by electrostatic interaction between heparin and the immobilized chitosan, which could be prepared within 1 hour. This coating prolonged the plasma re-calcification time (PRT) to over 60 minutes, effectively preventing surface-induced thrombosis. Favorable hemocompatibility was reflected in a hemolysis ratio of less than 2%, low levels of platelet adhesion and activation, and low levels of fibrinogen adhesion. We also systematically elucidate the anticoagulant mechanism of the coating, demonstrating why the coating can prevent thrombogenesis without the bleeding risk. Our work not only offers a promising and readily available heparin coating for blood-contact materials, but more importantly, the mechanism exploration supports the practical feasibility of heparin coating in various applications.