Coating Chemistry for Vessels

Demand for non-thrombogenic arterial conduits persists due to the poor clinical performance of existing synthetic grafts for small-diameter artery applications. Decellularized native and tissue-engineered vascular grafts have shown success in large-diameter vascular applications. The decellularization process necessary for the removal of cellular antigens also removes the endothelial cells (ECs) lining the lumen that is responsible for inhibiting coagulation and platelet adhesion. Following the removal of ECs, the damaged vascular wall contains exposed collagen, a highly thrombogenic surface, which in small-diameter vascular grafts activates platelets and blood coagulation proteins. Thus, one potential solution to preventing thrombus formation, subsequent occlusion and graft failure is to modify the decellularized vascular surfaces by “hiding” the exposed thrombogenic collagen with non-thrombogenic chemical structures such as heparan sulfate.

To avoid thrombogenic failure, the common approach used by others in the past has been the linking of heparin to decellularized grafts. Typically, heparin is linked to the extracellular matrix (ECM) using a “one-to-one” (one active group of ECM to one heparin chain) crosslinker such as glutaraldehyde or 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC). As there are few surface accessible amino groups on the ECM, the one-to-one approach results in a low surface coverage of heparin. In addition, heparin’s anticoagulant efficacy depends on its ability to bind antithrombin III (ATIII) through the appropriate presentation of its ATIII-specific pentasaccharide sequence. Lack of control over the heparin orientation, in combination with small amounts of heparin attachment, have been the main reasons for limited success following chemical immobilization of heparin on vascular grafts.

While directional coupling chemistry has been used to immobilize heparin to polymeric structures such as PTFE¹⁹ and nanomaterials, it has not been previously reported on dendrons/dendrimers or on biological structures. We are able to recreate the dense packing and relevant structural orientation by first amplifying the existing labile chemical groups using azide-clickable dendrons and then decorating the surface of the dendrons with end-on oriented heparin, which mimics the orientation of heparan sulfate on the EC surface.