Enhanced Prosthetic Vascular Graft Function by Local Release of Nitric Oxide

ABSTRACT Endograft infection, neointimal proliferation, and thrombosis are the three main clinical complications with ePTFE stent grafts affecting patients following endovascular arterial repair. These complicating factors often lead to restenosis, elevated risk for cardiac events, and device failure. Clinically available covered stent grafts are composed of porous hydrophobic polymeric (i.e., ePTFE) or bare metal surfaces that facilitate protein and cell- surface interactions leading to downstream cell accumulation, biofilm growth, and clinical complications. Current clinical standards include anticoagulation therapy before and after interventional procedures, while heparin- bonded stent grafts have shown moderate success at attenuating thrombosis. However, heparin-bonded stent grafts do not address infection and neointimal proliferation. There are no FDA-approved coated ePTFE products that can rigorously address all three complications – infection, neointimal proliferation, and thrombosis, in a single platform. We have recently demonstrated how nitric oxide (NO)-releasing polymer technologies can be integrated into medical devices to create highly biocompatible interfaces with the potential to prevent infection, proliferation, and thrombosis. NO is a multifaceted, endogenous gasotransmitter used by both the immune and cardiovascular systems to eradicate pathogens, disperse biofilms, maintain platelet quiescence, and regulate cell proliferation. By covalently attaching a synthetic NO donor (S-nitroso-N-acetylpenicillamine, SNAP) onto silicone rubber (PDMS), we can achieve NO-releasing materials (SNAP-PDMS) that exhibit >4 months of NO release at the blood-material interface to regulate these cellular processes. This enables a broad strategy against endograft infection, neointimal proliferation, and thrombosis, improving device patency and clinical outcomes. Therefore, the main objective of this STTR proposal is two develop endograft devices that integrate the SNAP- PDMS polymer technology to achieve long-term (> 30-d) release of NO at the device interface to reduce the incidence of infection, neointimal proliferation, and thrombosis all of which contribute to prosthetic graft failure.