076 A Clinical Study Investigating the Temporal Changes in Proteolytic Activity in Wounds Treated with Promogran*

The pathophysiology of wound repair is a delicately balanced, dynamic process involving both stimulatory and degradative factors to remove damaged tissue and synthesize new tissue. An imbalance of any of these factors may result in the formation of a chronic wound. Previous studies have indicated that the chronic wound environment is detrimental to cell and cytokine function, leading to delayed healing. The presence of a hostile chronic wound environment has been supported by many studies reporting elevated proteolytic activity in these wounds. However, it has not been determined if this elevation is due to an excess of a particular protease or a reduction in inhibitor levels. In this study we investigated the effect of PROMOGRANTM, a protease "modulating matrix, on wound healing in patients with venous leg ulcers and examined the effect on the wound environment. Wound fluid samples were collected from a number of patients throughout the course of treatment and both protease and inhibitor levels were analyzed. Our results indicate that wounds which respond to PROMOGRANTM also exhibited an overall decrease in human neutrophil-derived elastase and MMP activity. An increase in the ratio of alpha-1-antitrypsin to human neutrophil-derived elastase was also observed suggesting a greater degree of regulation post therapy, and a return to a more acute-like wound environment. Wounds that did not respond to this treatment demonstrated a greatly reduced ratio, signifying a persistent excess of proteolytic activity and a continued delay in healing. It is unclear whether the observed biochemical changes in the wound environment are responsible for healing or merely symptomatic of the disease state. We have, however, shown that an overall reduction in proteolytic activity is concomitant with healing. This suggests that therapies that redress the balance of inhibitor to protease may be beneficial in treatment of chronic wounds.