Attenuation of protease activity in chronic wound fluid with bisphosphonate-functionalised hydrogels
Article
Article Title | Attenuation of protease activity in chronic wound fluid with bisphosphonate-functionalised hydrogels |
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ERA Journal ID | 5035 |
Article Category | Article |
Authors | Rayment, Erin A. (Author), Dargaville, Tim R. (Author), Shooter, Gary K. (Author), George, Graeme A. (Author) and Upton, Zee (Author) |
Journal Title | Biomaterials |
Journal Citation | 29 (12), pp. 1785-1795 |
Number of Pages | 11 |
Year | 2008 |
Publisher | Elsevier |
Place of Publication | Amsterdam, Netherlands |
ISSN | 0142-9612 |
1878-5905 | |
Digital Object Identifier (DOI) | https://doi.org/10.1016/j.biomaterials.2007.12.043 |
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. |
Keywords | biocompatibility; hydrogel; matrix metalloproteinase; PHEMA; wound dressing; wound healing |
ANZSRC Field of Research 2020 | 321402. Clinical pharmacology and therapeutics |
320701. Medical bacteriology | |
320506. Medical biochemistry - proteins and peptides (incl. medical proteomics) | |
Public Notes | © 2008 Elsevier Ltd. Permanent restricted access to published version due to publisher copyright policy. |
Byline Affiliations | Queensland University of Technology |
Institution of Origin | University of Southern Queensland |
https://research.usq.edu.au/item/q2v82/attenuation-of-protease-activity-in-chronic-wound-fluid-with-bisphosphonate-functionalised-hydrogels
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