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Injectable nanoclay gels for angiogenesis

Injectable nanoclay gels for angiogenesis
Injectable nanoclay gels for angiogenesis

The retention and sustained activity of therapeutic proteins at delivery sites are goals of regenerative medicine. Vascular endothelial growth factor (VEGF) has significant potential in promoting the growth and regeneration of blood vessels but is intrinsically labile. This is exacerbated by the inflammatory microenvironments at sites requiring regeneration. For VEGF to be efficacious, it may require a carrier that stabilises it, protects it from degradation and retains it at the site of interest. In this study, we tested the hypothesis that injectable nanoclay gels comprising LaponiteTM XLG (a synthetic hectorite clay) can stabilise VEGF and retain it in the active form for therapeutic delivery. To achieve this, VEGF was incorporated in Laponite gels and its activity tested at a range of concentrations using in vitro cell culture tubulogenesis assays and in vivo angiogenesis assays. We found that VEGF-Laponite gels enhanced tubulogenesis in a dose-dependent manner in vitro. When administered subcutaneously in vivo, Laponite was retained at the injection site for up to a period of three weeks and promoted a 4-fold increase in blood vessel formation compared with that of alginate or vehicle controls as confirmed by CD31 staining. Notably, as compared to alginate, Laponite gels did not release VEGF, indicating a strong interaction between the growth factor and the nanoclay and suggesting that Laponite enhancement of VEGF efficacy is due to its retention at the implantation site for a prolonged period. Our approach provides a robust method for the delivery of bioactive recombinant VEGF without the necessity for complex hydrogel or protein engineering. In medicine, it is important to deliver drugs to a particular location in the body. Often, however, the drugs are quickly broken down and carried away in the blood before they can exert their effect. In this study, we used a type of synthetic clay, called LaponiteTM, to preserve a molecule, named VEGF, that stimulates the growth of blood vessels. Previously, we have been able to bind VEGF to the surface of clays, but the clay is not effective when injected or applied as a gel. Herein, we show that we can mix VEGF with the clay and that it strongly stimulates blood vessel growth. We speculate that this would be a useful material for skin wound healing.

1742-7061
378-387
Page, Daniel J.
56f3dd04-4037-4621-bbe8-e4198ca8d661
Clarkin, Claire E.
05cd2a88-1127-41aa-a29b-7ac323b4f3c9
Mani, Raj
a2455444-1b55-4ead-9836-f1e13c84172f
Khan, Najeed A.
1c06da81-592e-4db6-aef2-d55107d760b2
Dawson, Jonathan I.
b220fe76-498d-47be-9995-92da6c289cf3
Evans, Nicholas D.
06a05c97-bfed-4abb-9244-34ec9f4b4b95
Page, Daniel J.
56f3dd04-4037-4621-bbe8-e4198ca8d661
Clarkin, Claire E.
05cd2a88-1127-41aa-a29b-7ac323b4f3c9
Mani, Raj
a2455444-1b55-4ead-9836-f1e13c84172f
Khan, Najeed A.
1c06da81-592e-4db6-aef2-d55107d760b2
Dawson, Jonathan I.
b220fe76-498d-47be-9995-92da6c289cf3
Evans, Nicholas D.
06a05c97-bfed-4abb-9244-34ec9f4b4b95

Page, Daniel J., Clarkin, Claire E., Mani, Raj, Khan, Najeed A., Dawson, Jonathan I. and Evans, Nicholas D. (2019) Injectable nanoclay gels for angiogenesis. Acta Biomaterialia, 100, 378-387. (doi:10.1016/j.actbio.2019.09.023).

Record type: Article

Abstract

The retention and sustained activity of therapeutic proteins at delivery sites are goals of regenerative medicine. Vascular endothelial growth factor (VEGF) has significant potential in promoting the growth and regeneration of blood vessels but is intrinsically labile. This is exacerbated by the inflammatory microenvironments at sites requiring regeneration. For VEGF to be efficacious, it may require a carrier that stabilises it, protects it from degradation and retains it at the site of interest. In this study, we tested the hypothesis that injectable nanoclay gels comprising LaponiteTM XLG (a synthetic hectorite clay) can stabilise VEGF and retain it in the active form for therapeutic delivery. To achieve this, VEGF was incorporated in Laponite gels and its activity tested at a range of concentrations using in vitro cell culture tubulogenesis assays and in vivo angiogenesis assays. We found that VEGF-Laponite gels enhanced tubulogenesis in a dose-dependent manner in vitro. When administered subcutaneously in vivo, Laponite was retained at the injection site for up to a period of three weeks and promoted a 4-fold increase in blood vessel formation compared with that of alginate or vehicle controls as confirmed by CD31 staining. Notably, as compared to alginate, Laponite gels did not release VEGF, indicating a strong interaction between the growth factor and the nanoclay and suggesting that Laponite enhancement of VEGF efficacy is due to its retention at the implantation site for a prolonged period. Our approach provides a robust method for the delivery of bioactive recombinant VEGF without the necessity for complex hydrogel or protein engineering. In medicine, it is important to deliver drugs to a particular location in the body. Often, however, the drugs are quickly broken down and carried away in the blood before they can exert their effect. In this study, we used a type of synthetic clay, called LaponiteTM, to preserve a molecule, named VEGF, that stimulates the growth of blood vessels. Previously, we have been able to bind VEGF to the surface of clays, but the clay is not effective when injected or applied as a gel. Herein, we show that we can mix VEGF with the clay and that it strongly stimulates blood vessel growth. We speculate that this would be a useful material for skin wound healing.

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D Page 2019 - Accepted Manuscript
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More information

Accepted/In Press date: 15 September 2019
e-pub ahead of print date: 19 September 2019
Published date: December 2019

Identifiers

Local EPrints ID: 434620
URI: http://eprints.soton.ac.uk/id/eprint/434620
ISSN: 1742-7061
PURE UUID: a6e5fdba-342d-4673-8e2e-ba6f107b7508
ORCID for Jonathan I. Dawson: ORCID iD orcid.org/0000-0002-6712-0598

Catalogue record

Date deposited: 03 Oct 2019 16:30
Last modified: 26 Nov 2021 05:53

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Contributors

Author: Daniel J. Page
Author: Raj Mani
Author: Najeed A. Khan

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