In Vitro Studies to Show Sequestration of Matrix Metalloproteinases by Silver-Containing Wound Care Products

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Author(s): 
Michael Walker, PhD; Philip G. Bowler, M Phil; and Christine A. Cochrane, PhD

Hydrofiber® and AQUACEL® are registered trademarks of E.R. Squibb & Sons LCC. ConvaTec Wound Therapeutics™ is a trademark of E.R. Squibb & Sons LCC. All other trademarks are the property of their respective owners.

Delayed or compromised wound healing has, in part, been attributed to excess or “uncontrolled” proteinase activity in the wound bed. This has been supported by in vivo studies in which exudate from chronic leg ulcers1 and postoperative wound repair data2 have been analyzed. The family of matrix metalloproteinases (MMPs) comprises mostly zinc-based enzymes and includes generic classes such as collagenases, elastase, and gelatinases. They may be of endogenous (neutrophil or keratinocyte) or exogenous (bacterial) origin.3-6 The latter group includes collagenolytic enzymes found in many species, including common wound pathogens (eg, Pseudomonas aeruginosa and Staphylococcus aureus). Whatever the source, these enzymes degrade the extracellular matrix, which can lead to tissue destruction and the development of non-healing ulceration if activity is uncontrolled.7

Proteinases have been shown in in vivo studies to play a critical role in many of the physiologic processes involved in wound repair, including the early stages of clotting and inflammation, and later, clot lysis, fibroplasia, angiogenesis, and extracellular matrix remodeling.8-11 This proteolytic activity is tightly regulated in acute wounds to ensure a balance exists between tissue synthesis and tissue degradation with control occurring at the cellular and extracellular level (see Figure 1).

Breakdown in one or more of these control mechanisms may result in an increase in proteolytic activity (eg, by MMPs), which gives rise to immuno-pathology,12 a recognized condition in non-healing wounds.13 This is particularly true when exogenous proteinases produced by bacterial pathogens are present because these enzymes are not regulated by host inhibitors4 (see Figure 2).

Previous in vivo studies have shown increased activity of MMP-2 and MMP-9 in human chronic wound fluid14 and diabetic and venous ulcer tissue.15 Matrix metalloproteinases have been shown to play an important role during tissue repair processes.16 However, if uncontrolled and continually expressed (as occurs in chronic inflammation), it has been shown in pressure ulcer granulation tissue that these proteinases provide a destructive proteolytic environment that may inhibit healing and epidermal wound migration.16

References: 

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