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

Author:

Jiang Shouyuan1,Yang Nanji234,Tan Richard P.234,Moh Edward S. X.56,Fu Lu1,Packer Nicolle H.56,Whitelock John M.1,Wise Steven G.234,Rnjak‐Kovacina Jelena1,Lord Megan S.1ORCID

Affiliation:

1. Graduate School of Biomedical Engineering University of New South Wales Sydney NSW 2052 Australia

2. School of Medical Sciences Faculty of Health and Medicine University of Sydney Sydney NSW 2006 Australia

3. Charles Perkins Centre University of Sydney Sydney NSW 2006 Australia

4. The University of Sydney Nano Institute University of Sydney Sydney NSW 2006 Australia

5. ARC Centre of Excellence in Synthetic Biology Macquarie University Sydney New South Wales 2109 Australia

6. School of Natural Science Faculty of Science and Engineering Macquarie University Sydney New South Wales 2109 Australia

Abstract

AbstractSynthetic 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 remains an intractable challenge. Perlecan is the major heparan sulfate (HS) proteoglycan in the blood vessel wall with an inherent ability to regulate vascular cell activities associated with these major graft failure modes. Here the ability of the engineered form of perlecan domain V (rDV) to bind angiogenic growth factors is tuned and endothelial cell proliferation via the composition of its glycosaminoglycan (GAG) chain is supported. It is shown that the HS on rDV supports angiogenic growth factor signaling, including fibroblast growth factor (FGF) 2 and vascular endothelial growth factor (VEGF)165, while both HS and chondroitin sulfate on rDV are involved in VEGF189 signaling. It is also shown that physisorption of rDV on emerging electrospun silk fibroin vascular grafts promotes endothelialization and patency in a murine arterial interposition model, compared to the silk grafts alone. Together, this study demonstrates the potential of rDV as a tunable, angiogenic biomaterial coating that both potentiates growth factors and regulates endothelial cells.

Funder

Australian Research Council

National Heart Foundation of Australia

Publisher

Wiley

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