Use of Modified Superabsorbent Polymer Dressings for Protease Modulation in Improved Chronic Wound Care
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Index: WOUNDS. 2013;25(2):51–57.
Abstract: With more than 6 million patients affected with them in the United States, chronic ulcers represent one of the greatest problems in wound care. High levels of corrosive proteases, particularly matrix metalloproteinases (MMPs), within the wound environment are thought to contribute to the persistence of these wounds through denaturation of connective tissue proteins crucial to healing progression. Therefore, there is considerable interest in protease modulation using wound dressings to promote healing in chronic wounds. Such modulation could be achieved by direct absorption of proteases, by depleting co-factors within the wound, or by release of protease inhibitors. Method. The aim of this study is to examine protease modulation of a range of dressings with different chemistries, particularly those having demonstrated efficacy in chronic wound healing. Results. XTRASORB® HCS (dressing A) and XTRASORB® Foam (dressing B) were able to modulate proteases by both direct absorption of MMPs and depleting metal ion co-factors, and resulted in complete elimination of protease activity in the assay used. Duoderm® (dressing C) was able to modulate proteases by direct absorption only, and not by co-factor depletion. Promogran® (dressing D) was able to reduce MMP activity, but this was shown to be pH dependant, with any protease modulation being lost at neutral pH. Neither Allevyn® (dressing E) nor Vigilon® (dressing F) were able to modulate proteases by any mechanism. None of the protease modulating dressings acted through the release of protease inhibitors. Conclusion. Of the dressings studied, dressing A and dressing B were the most effective protease modulators due to their acting through 2 separate mechanisms.
Chronic ulcers are one of the greatest problems in wound management, with more than 6 million patients affected in the United States, and an annual cost in excess of $25 billion.1 Despite advances in wound care this situation continues to deteriorate, due to an aging population and the increase in prevalence of conditions linked to chronic ulcers, such as obesity, diabetes, and peripheral vascular disease.
It has long been recognized that chronic ulcers are associated with increased activity of proteases in wound fluids and tissues, with proteases, such as matrix metalloproteinases (MMPs), correlating with clinical status and poor healing potential.2 It is thought that protease-mediated destruction of important components of dermal connective tissues, such as collagen and fibronectin, is causal in the persistent nature of chronic wounds.3 In particular, MMP-9, which is an essential element in normal inflammation and tissue repair, is present at greatly elevated levels in ulcers, and this may contribute to the corrosive nature of the chronic wound environment. This has led to considerable interest in the possibility of protease modifying treatments in managing chronic ulcers.4,5
Activity of MMPs in the wound environment may be reduced either by their direct removal, by reducing cofactors essential for their function, such as metal ions, or by releasing components which inhibit their activity.6 Removal of proteases or their cofactors from the immediate wound environment are the preferred options, as release of inhibitory components may have detrimental effects beyond the target area, and hence presents both practical and regulatory difficulties.
There has been considerable interest in the use of protease modulating dressings that aim to reduce the levels or activity of corrosive proteases by removal of components within wound exudates.