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

Rayment, Erin A. and Dargaville, Tim R. and Shooter, Gary K. and George, Graeme A. and Upton, Zee (2008) Attenuation of protease activity in chronic wound fluid with bisphosphonate-functionalised hydrogels. Biomaterials, 29 (12). pp. 1785-1795. ISSN 0142-9612


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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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: © 2008 Elsevier Ltd. Permanent restricted access to published version due to publisher copyright policy.
Faculty/School / Institute/Centre: No Faculty
Faculty/School / Institute/Centre: No Faculty
Date Deposited: 06 Nov 2014 01:12
Last Modified: 11 Nov 2014 01:56
Uncontrolled Keywords: biocompatibility; hydrogel; matrix metalloproteinase; PHEMA; wound dressing; wound healing
Fields of Research (2008): 11 Medical and Health Sciences > 1115 Pharmacology and Pharmaceutical Sciences > 111502 Clinical Pharmacology and Therapeutics
11 Medical and Health Sciences > 1108 Medical Microbiology > 110801 Medical Bacteriology
11 Medical and Health Sciences > 1101 Medical Biochemistry and Metabolomics > 110106 Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics)
Fields of Research (2020): 32 BIOMEDICAL AND CLINICAL SCIENCES > 3214 Pharmacology and pharmaceutical sciences > 321402 Clinical pharmacology and therapeutics
32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320701 Medical bacteriology
32 BIOMEDICAL AND CLINICAL SCIENCES > 3205 Medical biochemistry and metabolomics > 320506 Medical biochemistry - proteins and peptides (incl. medical proteomics)
Socio-Economic Objectives (2008): C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920117 Skin and Related Disorders
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