Drug Refillable Vascular Grafts

Abstract

When dealing with cardiovascular disease, vascular devices are used to expand the vascular opening and maintain proper flow. However, current vascular grafts have a high rate of occlusion due to biological responses to the foreign body. By coating these devices with thrombomodulin (TM), an anti-clotting protein, the graft is protected from plaque accumulation. But since TM naturally degrades in the body over time, the risk of thrombosis is merely delayed. My project aims to mitigate the risk of long-term thrombosis for small diameter vascular grafts by providing a system to replenish the TM surface coating once it begins to degrade. In order to accomplish this, DNA was used as the homing mechanism and a process call DNA toehold exchange was utilized. By specially designing the sequence of primary and secondary strands of DNA, secondary strands bound to the drug or protein could displace one another from primary strands bound to the surface of the graft, resulting in the recoating of the surface with active drug. This process fully replaced the necessary amount of TM on the surface to prevent long-term thrombosis with over 100-fold excess. This high safety factor allows for more time between surface replacement procedures. This system can ultimately be applied to any system with a drug or protein coated surface, providing an effective means of sustained and controlled drug expression.