The goal of this project was to improve the long-term performance of clinical-grade expanded polytetrafluoroethylene (ePTFE) vascular grafts by coating them with a peptide ligand called LXW7. LXW7 is designed to bind circulating endothelial cells—the cells that normally line blood vessels—to the inner surface of the graft. By promoting endothelial cell attachment, the graft interior can better resemble a natural blood vessel, reducing rejection and blockage, which commonly occur with untreated ePTFE grafts recognized as foreign by the body.
The project began with optimization and validation of the LXW7 chemical coating on medical-grade ePTFE grafts. We confirmed successful attachment of LXW7 to the graft surface and measured coating thickness. In cell culture experiments, LXW7-coated grafts showed improved endothelial cell attachment and growth, were non-toxic, and demonstrated durability for over 100 days under exposure to blood serum. These findings confirmed enhanced biocompatibility and long-lasting coating stability.
Next, the coated grafts were tested in a rat carotid artery model using small-diameter (~1 mm) ePTFE grafts. A total of 49 rats were divided across three time points (1, 2, and 6 weeks), with each group receiving either an LXW7-coated or untreated graft. Doppler ultrasound confirmed graft patency immediately after implantation and was performed again at study endpoints to determine if the grafts stayed open. Results showed no significant differences in overall graft patency between LXW7-treated and untreated grafts at any time point. However, histological analysis revealed significantly less blockage in LXW7-treated grafts at the 1-week time point, though this difference was not maintained at 2 or 6 weeks.
An additional experiment used an artificial perfusion system that pumped artificial blood containing human endothelial cells through the grafts in an “outside the body” perfusion system. This system mimicked physiological blood flow conditions. LXW7-coated grafts demonstrated superior binding of circulating human endothelial cells compared to untreated grafts, further supporting the coating’s biological function.
Finally, the effectiveness of LXW7-coated grafts was evaluated in a large animal sheep model. Commercial ePTFE grafts, both untreated and LXW7-coated, were implanted bilaterally between the carotid artery and jugular vein in eight sheep. The animals received antiplatelet therapy and were monitored for six months using monthly Doppler ultrasound. Early results showed higher patency in LXW7 grafts at 6 weeks, though by 5 and 6 months patency rates were similar between groups. Histological analysis at study completion showed significantly less blockage in LXW7-treated grafts, particularly at the outflow region. Scanning electron microscopy revealed increased endothelial cell coverage and reduced platelet adhesion on LXW7-coated grafts.
Overall, the study demonstrated that LXW7 coating enhances endothelial cell attachment and reduces graft blockage, especially in early and long-term tissue responses, supporting its potential to improve vascular graft performance.