Targeting matrix metalloproteases to improve cutaneous wound healing

Abstract

Wound repair is a physiological event in which tissue injury initiates a repair process leading to restoration of structure and function of the tissue. Cutaneous wound repair can be divided into a series of overlapping phases including formation of fibrin clot, inflammatory response, granulation tissue formation incorporating re-epithelialisation and angiogenesis and finally, matrix formation and remodelling. Matrix metalloproteases (MMPs) are a family of neutral proteases that play a vital role throughout the entire wound healing process. They regulate inflammation, degrade the extracellular matrix (ECM) to facilitate the migration of cells and remodel the new ECM. However, excessive MMP activity contributes to the development of chronic wounds. Selective control of MMP activity may prove to be a valuable therapeutic approach to promote healing of chronic ulcers. Recent evidence indicates that the anticoagulant, activated protein C may be useful in the treatment of non-healing wounds by preventing excessive protease activity through inhibition of inflammation and selectively increasing MMP-2 activity to enhance angiogenesis and re-epithelialisation.