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Attenuation of protease activity in chronic wound fluid (CWF) with bisphosphonate-functionalised hydrogels

Rayment, Erin A., Dargaville, Tim R., Shooter, Gary K., George, Graeme A., & Upton, Zee (2008) Attenuation of protease activity in chronic wound fluid (CWF) with bisphosphonate-functionalised hydrogels. Biomaterials, 29(12), pp. 1785-1795.

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Abstract

Chronic ulcers are an important and costly medical issue, imposing considerable pain, reduced mobility and decreased quality of life. The common pathology in these chronic wounds is excessive proteolytic activity, resulting in degradation of key factors critical to the ulcer's ability to heal. Matrix metalloproteinases (MMPs), a large family of zinc-dependent endopeptidases, have been shown to have increased activity in chronic wound fluid (CWF), with many authors suggesting that they need to be inhibited for the ulcer to heal. The studies we report here show that the excessive MMP activity in CWF can be inhibited with the bisphosphonate alendronate, in the form of a sodium salt, a functionalised analogue, and tethered to a poly(2-hydroxy methacrylate) (PHEMA) hydrogel. Furthermore, these functionalised alendronate hydrogels appear to be biologically inert as assessed in a three-dimensional ex vivo human skin equivalent model. Together, these results highlight the potential use of a tethered MMP inhibitor to inhibit protease activity in wound fluid. This approach may improve wound healing as it still allows MMPs to remain active in the upper cellular layers of the ulcer bed where they perform vital roles in wound healing; thus may offer an attractive new device-orientated wound therapy.

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ID Code: 13684
Item Type: Journal Article
Keywords: Wound healing, Wound dressing, Matrix metalloproteinase, PHEMA, Hydrogel, Biocompatibility, tissue repair and regeneration, upton, rayment, dargaville, shooter, george
DOI: 10.1016/j.biomaterials.2007.12.043
ISSN: 0142-9612
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Biochemistry and Cell Biology not elsewhere classified (060199)
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2008 Elsevier
Copyright Statement: Reproduced in accordance with the copyright policy of the publisher.
Deposited On: 10 Jun 2008
Last Modified: 29 Feb 2012 23:51

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