Chronic wound fluid--thinking outside the box

Chronic wounds are associated with an altered wound milieu that results from an imbalance in extracellular matrix (ECM) homeostasis. This alteration is characterized by an increased destruction and degradation of components of the ECM with a concomitant lack of synthesis of these elements. Traditionally wound fluid has been considered a reflection of the internal wound milieu. It has been used to monitor and reflect on the chronic status of a wound or to measure the efficacy of wound treatment. However, on closer inspection of chronic wound fluid, certain components of the fluid, particularly matrix metalloproteinases (MMPs) and their subcomponents (MMP-9) have been found to exist at higher levels in wound fluid than in the corresponding wound. There is mounting evidence that much of the destructive effects observed in chronic wounds may be compounded by components of the wound exudate which are corrosive in nature resulting in a continuum of ECM breakdown. Isolation of these components has identified MMPs, in particular MMP-9 as dominant in this destructive process. Additionally an association has been made between high bacterial levels and elevated MMP9 in chronic wounds. Agents that have efficacy against MMP-9 and significant antibacterial potency thus provide a dual defense against chronic wounds. It is likely that these agents cause a change in the chronic wound fluid components that more closely resemble the balance of proteases and growth factors seen acute wounds, thus triggering a positive wound healing process. Nanocrystalline silver appears to fulfill these criteria. A strategy is suggested whereby wound fluid is directly targeted to diminish the corrosive wound fluid elements in an attempt to break the ongoing destructive inflammatory cycle. This presents a relatively new treatment paradigm attempting to influence wound healing by working from without to initiate changes within.