Reduced Thrombus Formation by Hyaluronic Acid Coating of Endovascular Devices

Abstract

Abstract —Biocompatible stent coatings may alleviate problems of increased (sub)acute thrombosis after stent implantation. Hyaluronic acid (HA), a ubiquitous, nonsulfated glycosaminoglycan, inhibits platelet adhesion and aggregation and prolongs bleeding when administered systemically. However, the effects of immobilized HA for reducing stent platelet deposition in vivo are unknown. We therefore quantified the antithrombotic effects of coating stainless steel stents and tubes with HA using an established baboon thrombosis model under physiologically relevant blood flow conditions. HA-coated and uncoated (control) stents (3.5 mm in diameter, n=32) and stainless steel tubes (4.0 mm in diameter, n=18) were deployed into exteriorized arteriovenous shunts of conscious, nonanticoagulated baboons. Accumulation of 111 In-radiolabeled platelets was quantified by continuous gamma-camera imaging during a 2-hour blood exposure period. HA coating resulted in a significant reduction in platelet deposition in long (4 cm) tubes (0.24±0.15×10 9 versus 6.12±0.49×10 9 platelets; P <0.03), short (2 cm) stainless steel tubes (0.18±0.06×10 9 versus 3.03±0.56×10 9 platelets; P <0.008), and stents (0.82±0.20×10 9 versus 1.83±0.23×10 9 platelets; P <0.02) compared with uncoated control devices. Thus, HA coating reduces platelet thrombus formation on stainless steel stents and tubes in primate thrombosis models. These results indicate that immobilized HA may represent an attractive strategy for improving the thromboresistance of endovascular devices.