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

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^*

^*Corresponding author for this work

School of Natural Sciences

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

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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.

Original language	English
Pages (from-to)	184-196
Number of pages	13
Journal	Journal of Controlled Release
Volume	362
Early online date	31 Aug 2023
DOIs	https://doi.org/10.1016/j.jconrel.2023.08.052
Publication status	Published - Oct 2023

Bibliographical note

Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

angiogenesis
biomaterials
growth factors
perlecan
vascularisation
wound healing

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10.1016/j.jconrel.2023.08.052Licence: CC BY-NC

Publisher version (open access)Final published version, 11.8 MBLicence: CC BY-NC

Cite this

Kim, H. N., Elgundi, Z., Lin, X., Fu, L., Tang, F., Moh, E. S. X., Jung, M., Chandrasekar, K., Bartlett-Tomasetig, F., Foster, C., Packer, N. H., Whitelock, J. M., Rnjak-Kovacina, J., & Lord, M. S. (2023). Engineered short forms of perlecan enhance angiogenesis by potentiating growth factor signalling. Journal of Controlled Release, 362, 184-196. https://doi.org/10.1016/j.jconrel.2023.08.052

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title = "Engineered short forms of perlecan enhance angiogenesis by potentiating growth factor signalling",

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 factors, perlecan, vascularisation, wound healing",

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

note = "Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2023",

month = oct,

doi = "10.1016/j.jconrel.2023.08.052",

language = "English",

volume = "362",

pages = "184--196",

journal = "Journal of Controlled Release",

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Kim, HN, Elgundi, Z, Lin, X, Fu, L, Tang, F, Moh, ESX, Jung, M, Chandrasekar, K, Bartlett-Tomasetig, F, Foster, C, Packer, NH, Whitelock, JM, Rnjak-Kovacina, J & Lord, MS 2023, 'Engineered short forms of perlecan enhance angiogenesis by potentiating growth factor signalling', Journal of Controlled Release, vol. 362, pp. 184-196. https://doi.org/10.1016/j.jconrel.2023.08.052

TY - JOUR

T1 - Engineered short forms of perlecan enhance angiogenesis by potentiating growth factor signalling

AU - Kim, Ha Na

AU - Elgundi, Zehra

AU - Lin, Xiaoting

AU - Fu, Lu

AU - Tang, Fengying

AU - Moh, Edward S. X.

AU - Jung, MoonSun

AU - Chandrasekar, Keerthana

AU - Bartlett-Tomasetig, Florence

AU - Foster, Candice

AU - Packer, Nicolle H.

AU - Whitelock, John M.

AU - Rnjak-Kovacina, Jelena

AU - Lord, Megan S.

N1 - Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2023/10

Y1 - 2023/10

N2 - 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.

AB - 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.

KW - angiogenesis

KW - biomaterials

KW - growth factors

KW - perlecan

KW - vascularisation

KW - wound healing

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DO - 10.1016/j.jconrel.2023.08.052

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SN - 0168-3659

VL - 362

SP - 184

EP - 196

JO - Journal of Controlled Release

JF - Journal of Controlled Release

ER -

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

Abstract

Bibliographical note

Keywords

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COESB: ARC Centre of Excellence in Synthetic Biology

Cite this

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

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Projects

COESB: ARC Centre of Excellence in Synthetic Biology

Cite this