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조회314

김하나Ha Na Kim

University of New South Wales

J. Control. Release, Volume 362, October 2023, Pages 184-196 | https://doi.org/10.1016/j.jconrel.2023.08.052 Engineered short forms of perlecan enhance angiogenesis by potentiating growth factor signalling.

Ha Na Kim ^a,b, Zehra Elgundi ^a, Xiaoting Lin ^a, Lu Fu ^a, Fengying Tang ^a,c, Edward S.X. Moh ^d,e, MoonSun Jung ^a, Keerthana Chandrasekar ^a, Florence Bartlett-Tomasetig ^f, Candice Foster ^a, Nicolle H. Packer ^d,e, John M. Whitelock ^a, Jelena Rnjak-Kovacina ^a,g, Megan S. Lord ^a

^aGraduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia

^bMolecular Surface Interaction Laboratory, Analytical Centre, University of New South Wales, Sydney, NSW 2052, Australia

^cComparative Pathology Program, Department of Comparative Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA

^dARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, New South Wales 2109, Australia

^eSchool of Natural Science, Faculty of Science and Engineering, Macquarie University, Sydney, New South Wales 2109, Australia

^fKatherina Gaus Light Microscopy Facility, Analytical Centre, University of New South Wales, Sydney, NSW 2052, Australia

^gTyree Institute of Health Engineering, University of New South Wales, Sydney, NSW 2052, Australia

Corresponding author : Megan S. Lord

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.

논문정보

형식Research article
게재일2023년 10월 (BRIC 등록일 2023-09-15)
연구진국외 연구진
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