Plasma-Polymerized Nanoparticles Presenting Fibrillin-1 Drive Rapid Re-Endothelialization of Vascular Grafts.

Abstract

Small diameter vascular grafts made from expanded polytetrafluoroethylene (ePTFE) dominate clinical practice but are prone to high failure rates due to poor endothelialization, acute thrombosis or mid-term neointimal hyperplasia. The highly hydrophobic surface of ePTFE inhibits endothelial cell attachment and proliferation, making timely recovery of the protective endothelial layer a key challenge. Chemically inert, highly hydrophobic polymers such as ePTFE are amongst the most difficult to improve with biofunctionalization. To address this, a novel surface coating comprising a new class of plasma polymerized nanoparticles (PPN) functionalized with bioactive PF8, a recombinant fibrillin-1 peptide is developed. PPN surface modification significantly reduces ePTFE hydrophobicity, enabling efficient surface coating of PPN-PF8 and promoting endothelial attachment and proliferation in vitro. In a rat abdominal aortic interposition model, PPN-PF8 functionalized ePTFE grafts rapidly re-endothelialized, with extensive coverage of endothelial cells at 3 weeks post-implantation. This leads to increased tissue plasminogen activator (tPA) secretion and reduced fibrin deposition, indicating the formation of a healthy, functional endothelial layer. These findings highlight the potential of plasma-polymerized nanoparticles presenting fibrillin-1 to drive rapid re-endothelialization, offering an accessible and scalable method for improving the performance of small-diameter vascular grafts.