Various anticoagulants have been used to improve the hemocompatibility of vascular grafts such as heparin, corn trypsin inhibitor, as well as direct thrombin inhibitors such as hirudin, bivalirudin, and argatroban. Among these, heparin is the most widely used agent. Heparin acts as an anticoagulant by binding to antithrombin and accelerating the rate at which it inhibits thrombin, factor Xa and other coagulation proteases (Figure ). Various techniques have been used to immobilize heparin on surfaces including covalent attachment, physical adsorption, electrostatic attachment, and layer-by-layer deposition. Covalent attachment of heparin is the preferred method because each heparin molecule possesses several free carboxyl groups that enable covalent bonds with functional groups on the biomaterial such as amino or hydroxyl groups. However, the efficacy of the immobilized heparin can be compromised because the multiple covalent linkages limit its capacity to bind to antithrombin. End-point immobilization of heparin reduces this problem and materials coated with heparin using this technique exhibit less platelet adhesion and clot formation compared with materials coated with heparin via multivalent techniques. Several heparin coated grafts are currently available including Gore® and Gentige®, which are fabricated from ePTFE and Dacron, respectively. However, the applicability of these grafts is hindered by the short half-life of the immobilized heparin. The half-life of heparin may be prolonged by using "sandwiched" layer-by-layer surface coating methods. For example, when an electro-spun polycaprolactone vascular graft was modified with polyethyleneimine and heparin using catechol/gallol surface chemistry, there was more heparin on the surface compared with other conventional layer-by-layer coating methods and the graft's capacity to resist platelet and fibrinogen adhesion were prolonged. Endogenous anticoagulant agents have been extensively explored for use in anticoagulant coatings. Anticoagulant proteins such as tissue factor pathway inhibitor and protein C exhibit thromboresistance in vitro, however their bioactivity was compromised by the sterilization process.