Truncated vascular endothelial cadherin enhances rapid endothelialization of small diameter synthetic vascular grafts

Bob S.L. Lee; Nianji. Yang; Miguel. Santos; Matthew J. Moore; Angus J. Grant; Jun-Hyeog Jang; Behnam Akhavan; Marcela M. Bilek; Richard P. Tan; Steven G. Wise

Materials Today Advances (Jun 2022)

Truncated vascular endothelial cadherin enhances rapid endothelialization of small diameter synthetic vascular grafts

Bob S.L. Lee,
Nianji. Yang,
Miguel. Santos,
Matthew J. Moore,
Angus J. Grant,
Jun-Hyeog Jang,
Behnam Akhavan,
Marcela M. Bilek,
Richard P. Tan,
Steven G. Wise

Affiliations

Bob S.L. Lee: School of Medical Sciences, Faculty of Health and Medicine, University of Sydney, NSW, 2006, Australia; Charles Perkins Centre, University of Sydney, NSW, 2006, Australia
Nianji. Yang: School of Medical Sciences, Faculty of Health and Medicine, University of Sydney, NSW, 2006, Australia; Charles Perkins Centre, University of Sydney, NSW, 2006, Australia
Miguel. Santos: School of Medical Sciences, Faculty of Health and Medicine, University of Sydney, NSW, 2006, Australia; Charles Perkins Centre, University of Sydney, NSW, 2006, Australia
Matthew J. Moore: School of Medical Sciences, Faculty of Health and Medicine, University of Sydney, NSW, 2006, Australia; Charles Perkins Centre, University of Sydney, NSW, 2006, Australia
Angus J. Grant: School of Medical Sciences, Faculty of Health and Medicine, University of Sydney, NSW, 2006, Australia; Charles Perkins Centre, University of Sydney, NSW, 2006, Australia
Jun-Hyeog Jang: Department of Biochemistry, College of Medicine, Inha University, Incheon, 400-712, South Korea
Behnam Akhavan: School of Physics, University of Sydney, NSW, 2006, Australia; School of Biomedical Engineering, University of Sydney, NSW, 2006, Australia
Marcela M. Bilek: Charles Perkins Centre, University of Sydney, NSW, 2006, Australia; Sydney Nano Institute, The University of Sydney, NSW, 2006, Australia; School of Physics, University of Sydney, NSW, 2006, Australia; School of Biomedical Engineering, University of Sydney, NSW, 2006, Australia
Richard P. Tan: School of Medical Sciences, Faculty of Health and Medicine, University of Sydney, NSW, 2006, Australia; Charles Perkins Centre, University of Sydney, NSW, 2006, Australia
Steven G. Wise: School of Medical Sciences, Faculty of Health and Medicine, University of Sydney, NSW, 2006, Australia; Charles Perkins Centre, University of Sydney, NSW, 2006, Australia; Sydney Nano Institute, The University of Sydney, NSW, 2006, Australia; Corresponding author. A/Prof Steven Wise Charles Perkins Centre John Hopkins Dr., Camperdown, NSW, 2006, Australia.

Journal volume & issue: Vol. 14
p. 100222

Abstract

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Complete and rapid endothelialization is critical to the long-term performance of synthetic vascular grafts. A fully formed endothelium is resistant to thrombosis and mitigates the development of neointimal hyperplasia, the dominant modes of acute and chronic graft failure, respectively. Significant research efforts aim to develop strategies which enhance graft endothelialization through the incorporation of surface ligands that promote the attachment and growth of endothelial cells. In native vessels these functions are regulated by the adhesion molecule vascular endothelial cadherin (VE-Cad). VE-Cad is exclusive to endothelial cells and possesses high self-affinity, forming homodimers with VE-Cad on adjacent endothelial cells. Leveraging this targeted binding ability, we developed a graft functionalization approach using a recombinant truncated form of VE-Cad (VEtr). VEtr contains only the domains responsible for self-interaction, recognition and adhesion. Using the plasma functionalization technique, plasma immersion ion implantation (PIII) technique we immobilize VEtr onto the surface of electrospun polycaprolactone (PCL). VEtr scaffolds achieved a nearly 2-fold increase in attachment and spreading, and a 2.5-fold increase in proliferation of human coronary artery endothelial cells (HCAECs) compared with control scaffolds in vitro. Following 14-day implantation in a mouse carotid artery model, VEtr grafts showed ∼90% CD31-positive endothelial coverage. The benefits of this enhanced endothelialization included an ∼88% reduction in fibrin deposition (early thrombosis) as well as ∼63% reduction in macrophage recruitment (early neointimal hyperplasia). These findings highlight VEtr functionalization as a promising approach for rapid graft endothelialization which may potentially improve the long-term performance of synthetic vascular grafts.

Published in Materials Today Advances

ISSN: 2590-0498 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials
Website: https://www.journals.elsevier.com/materials-today-advances

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