Tuning Recombinant Perlecan Domain V to Regulate Angiogenic Growth Factors and Enhance Endothelialization of Electrospun Silk Vascular Grafts

Abstract

Synthetic vascular grafts are used to bypass significant arterial blockage when native blood vessels are unsuitable, yet their propensity to fail due to poor blood compatibility and progressive graft stenosis remain an intractable challenge. Perlecan is the major heparan sulphate (HS) proteoglycan in the blood vessel wall with an inherent ability to regulate vascular cell activities associated with these major graft failure modes. Here we tune the ability of the engineered form of perlecan domain V (rDV) to bind angiogenic growth factors and support endothelial cell proliferation via the composition of its glycosaminoglycan chain. We show that the HS on rDV supports angiogenic growth factor signalling, including fibroblast growth factor 2 and vascular endothelial growth factor (VEGF)165, while both HS and chondroitin sulphate on rDV are involved in VEGF189 signalling. We also show that physisorption of rDV on emerging electrospun silk fibroin vascular grafts promote endothelialisation and patency in a murine arterial interposition model, compared to the silk grafts alone. Together, this study demonstrates the potential of rDV as a tuneable, angiogenic biomaterial coating which both potentiates growth factors and regulates endothelial cells.This article is protected by copyright. All rights reserved