The role of endogenous and exogenous enzymes in chronic wounds: A focus on the implications of aberrant levels of both host and bacterial proteases in wound healing

Abstract

Cutaneous wound healing is orchestrated by a number of physiological pathways that ultimately lead to reformation of skin integrity and the production of functional scar tissue. The remodeling of a wound is significantly affected by matrix metalloproteinases (MMPs), which act to control the degradation of the extracellular matrix (ECM). Regulation of MMPs is imperative for wound healing as excessive levels of MMPs can lead to disproportionate destruction of the wound ECM compared to ECM deposition. In addition to human MMPs, bacterial proteases have been found to be influential in tissue breakdown and, as such, have a role to play in the healing of infected wounds. For example, the zinc-metalloproteinase, elastase, produced by Pseudomonas aeruginosa, induces degradation of fibroblast proteins and proteoglycans in chronic wounds and has also been shown to degrade host immune cell mediators. Microbial extracellular enzymes have also been shown to degrade human wound fluid and inhibit fibroblast cell growth. It is now being acknowledged that host and bacterial MMPs may act synergistically to cause tissue breakdown within the wound bed. Several studies have suggested that bacterial-derived secreted proteases may act to up-regulate the levels of MMPs produced by the host cells. Together, these findings indicate that bacterial phenotype in terms of protease producing potential of bacteria should be taken into consideration during diagnostic and clinical intervention of infected wound management. Furthermore, both host MMPs and those derived from infecting bacteria need to be targeted in order to increase the healing capacity of the injured tissue. The aim of this review is to investigate the evidence suggestive of a relationship between unregulated levels of both host and bacterial proteases and delayed wound healing.

Choosing a Wound Dressing Based on Common Wound Characteristics

“…3,33 Studies have shown that chronic wound fluid contains elevated protease levels known to have deleterious effects, such as the degradation of de novo granulation tissue and endogenous biologically active proteins such as growth factors and cytokines. 34,35 Protease-lowering dressings have demonstrated efficacy at removing slough, promoting granulation tissue formation, and stimulating wound repair. CHOOSING THE CORRECT WOUND DRESSING 37 An example of a protease-lowering dressing is the phosphorylated cotton wound dressings prepared to target sequestration of proteases from chronic wound exudate through a cationic uptake binding mechanism involving salt bridge formation of the positively charged amino acid side chains of proteases with the phosphate counter-ions of the wound dressing fiber.…”

Proteases and Delayed Wound Healing

“…3,26 Protease activity is essential for cutaneous wound healing, as demonstrated by the retarded wound healing seen in mice deficient in plasminogen, the serine protease precursor, and mice treated with a metalloprotease inhibitor. 9 Neutrophil elastase has also demonstrated antimicrobial properties against a range of wound-associated bacteria.…”

Ulcer Piercing: A Novel Drainage Technique for Diabetic Patients with Complicated Foot

“…Excessive inflammation due to the persistence of a critical bacterial contamination, biofilm or infection leads to wound chronicity [4]. Stalling of ulcer healing, which do not progress beyond the inflammatory phase, has been related to persistent inflammation [5] and an increase of matrix metalloproteases and elastase activities [6,7] . .…”