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

Autor: Kim HN; 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., Elgundi Z; Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia., Lin X; Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia., Fu L; Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia., Tang F; 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., Moh ESX; 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., Jung M; Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia., Chandrasekar K; Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia., Bartlett-Tomasetig F; Katherina Gaus Light Microscopy Facility, Analytical Centre, University of New South Wales, Sydney, NSW 2052, Australia., Foster C; Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia., Packer NH; 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., Whitelock JM; Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia., Rnjak-Kovacina J; 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., Lord MS; Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: m.lord@unsw.edu.au.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2023 Oct; Vol. 362, pp. 184-196. Date of Electronic Publication: 2023 Aug 31.
DOI: 10.1016/j.jconrel.2023.08.052
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare no competing interest.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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