Mechanism of action of PROMOGRAN, a protease modulating matrix, for the treatment of diabetic foot ulcers

TLDR

Proteases are essential for wound repair, yet uncontrolled activity in chronic wounds degrades granulation tissue and growth factors, contributing to tissue damage. The study proposes that correcting the proteolytic imbalance in chronic wounds could be an effective therapeutic strategy. Using an ex vivo wound fluid model, the proprietary treatment was shown to bind and inactivate proteases. In diabetic foot ulcer wound fluid, the treatment significantly lowered neutrophil elastase, plasmin, and MMP activities versus wet gauze, supporting its role in modifying the microenvironment to promote granulation and repair.

Abstract

Proteases play a critical role in many of the physiologic processes of wound repair. However, if their activity becomes uncontrolled proteases can mediate devastating tissue damage and consequently they have been implicated in chronic wound pathophysiology. Previous studies have shown that chronic wound fluid contains elevated protease levels that have deleterious effects, degrading de novo granulation tissue and endogenous biologically active proteins such as growth factors and cytokines. Therefore, we have proposed that an effective therapeutic approach for chronic wounds would be to modify this hostile environment and redress this proteolytic imbalance. Using an ex vivo wound fluid model, we show the ability of a proprietary new wound treatment to bind and inactivate proteases. We have shown that the addition of this test material to human chronic wound fluid obtained from diabetic foot ulcer patients resulted in a significant reduction in the activities of neutrophil‐derived elastase, plasmin, and matrix metalloproteinase when compared to wet gauze. This study provides mechanistic evidence to support the hypothesis that this novel treatment modality for chronic wounds physically modifies the wound microenvironment, and thereby promotes granulation tissue formation and stimulates wound repair.