Engineered short forms of perlecan enhance angiogenesis by potentiating growth factor signalling

Ha Na Kim; Zehra Elgundi; Xiaoting Lin; Lu Fu; Fengying Tang; Edward S X Moh; MoonSun Jung; Keerthana Chandrasekar; Florence Bartlett-Tomasetig; Candice Foster; Nicolle H Packer; John M Whitelock; Jelena Rnjak-Kovacina; Megan S Lord

doi:10.1016/j.jconrel.2023.08.052

Engineered short forms of perlecan enhance angiogenesis by potentiating growth factor signalling

J Control Release. 2023 Oct:362:184-196. doi: 10.1016/j.jconrel.2023.08.052. Epub 2023 Aug 31.

Affiliations

¹ Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia; Molecular Surface Interaction Laboratory, Analytical Centre, University of New South Wales, Sydney, NSW 2052, Australia.
² Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
³ Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia; Comparative Pathology Program, Department of Comparative Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
⁴ ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, New South Wales 2109, Australia; School of Natural Science, Faculty of Science and Engineering, Macquarie University, Sydney, New South Wales 2109, Australia.
⁵ Katherina Gaus Light Microscopy Facility, Analytical Centre, University of New South Wales, Sydney, NSW 2052, Australia.
⁶ Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia; Tyree Institute of Health Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
⁷ Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: m.lord@unsw.edu.au.

PMID: 37648081
DOI: 10.1016/j.jconrel.2023.08.052

Abstract

Growth factors are key molecules involved in angiogenesis, a process critical for tissue repair and regeneration. Despite the potential of growth factor delivery to stimulate angiogenesis, limited clinical success has been achieved with this approach. Growth factors interact with the extracellular matrix (ECM), and particularly heparan sulphate (HS), to bind and potentiate their signalling. Here we show that engineered short forms of perlecan, the major HS proteoglycan of the vascular ECM, bind and signal angiogenic growth factors, including fibroblast growth factor 2 and vascular endothelial growth factor-A. We also show that engineered short forms of perlecan delivered in porous chitosan biomaterial scaffolds promote angiogenesis in a rat full thickness dermal wound model, with the fusion of perlecan domains I and V leading to superior vascularisation compared to native endothelial perlecan or chitosan scaffolds alone. Together, this study demonstrates the potential of engineered short forms of perlecan delivered in chitosan scaffolds as next generation angiogenic therapies which exert biological activity via the potentiation of growth factors.

Keywords: Angiogenesis; Biomaterials; Growth factor; Perlecan; Vascularisation; Wound healing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chitosan*
Extracellular Matrix Proteins
Heparan Sulfate Proteoglycans / metabolism
Rats
Vascular Endothelial Growth Factor A* / genetics
Vascular Endothelial Growth Factor A* / metabolism

Substances

perlecan
Vascular Endothelial Growth Factor A
Chitosan
Heparan Sulfate Proteoglycans
Extracellular Matrix Proteins