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A hydrogen tethered inhibitor of matrix metalloproteinases

Cao, Yang, Croll, Tristan I., Shooter, Gary K., Upton, Zee, & Dargaville, Tim R. (2010) A hydrogen tethered inhibitor of matrix metalloproteinases. In 20th Annual Australasian Society for Biomaterials and Tissue Engineering Conference, 10th - 12th February 2010, Brisbane, Queensland. (Unpublished)

Abstract

During wound repair, the balance between matrix metalloproteinases (MMPs) and their natural inhibitors (the TIMPs) is crucial for the normal extra cellular matrix turnover. However, the over expression of several MMPs including MMP-1, 2, 3, 8, 9 and MMP-10, combined with abnormally high levels of activation or low expression of TIMPs, may contribute to excessive degradation of connective tissue and formation of chronic ulcers. There are many groups exploring strategies for promoting wound healing involving delivery of growth factors, cells, ECM components and small molecules. Our approach for improving the balance of MMPs is not to add anything more to the wound, but instead to neutralise the over-expressed MMPs using inhibitors tethered to a bandage-like hydrogel. Our in vitro experiments using designed synthetic pseudo peptide inhibitors have been demonstrated to inhibit MMP activity in standard solutions. These inhibitors have also been tethered to polyethylene glycol hydrogels using a facile reaction between the linker unit on the inhibitor and the gel. After tethering the inhibition of MMPs diminishes to some extent and we postulate that this arises due to poor diffusion of the MMPs into the gels. When the tethered inhibitors were tested against chronic wound fluid obtained against patients we observed over 40% inhibition in proteolytic activity suggesting our approach may prove useful in rebalancing MMPs within chronic wounds.

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ID Code: 33126
Item Type: Conference Item (Poster)
Additional URLs:
Keywords: matrix metalloproteinase inhibitor, polyethylene glycol, hydrogel, chronic wound fluid, hydroxamic acid
Subjects: Australian and New Zealand Standard Research Classification > ENGINEERING (090000) > BIOMEDICAL ENGINEERING (090300) > Biomaterials (090301)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > PUBLIC HEALTH AND HEALTH SERVICES (111700) > Aged Health Care (111702)
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2010 [please consult the authors]
Deposited On: 15 Jul 2010 08:16
Last Modified: 18 May 2011 00:56

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