Proteases and Delayed Wound Healing

Significance: Proteases and their inhibitors contribute to the balance between extracellular matrix (ECM) degradation and deposition, creating an equilibrium that is essential for the timely and coordinated healing of cutaneous wounds. However, when this balance is disrupted, wounds are led into a state of chronicity characterized by abundant levels of proteases and decreased levels of protease inhibitors. Recent Advances: Researchers have sought to investigate the roles of proteases within both acute and chronic wounds and how the manipulation of protease activity may aid healing. Indeed, numerous wound dressings have been developed that target such proteases in an attempt to promote wound healing. Critical Issues: The normal tissue response to injury involves a complex interaction between cells and cellular mediators. In particular, the inflammatory response is augmented in chronic wounds which are characterized by elevated levels of proinflammatory cytokines and proteases. While controlling levels of inflammation and protease expression is a critical part of normal wound healing, elevated and prolonged expression of proteases produced during the inflammatory phase of healing can lead to excessive ECM degradation associated with impaired healing. Future Directions: It seems plausible that future research should aim to investigate the ways in which proteases may be targeted as an alternative therapeutic approach to wound management and to assess the benefits and draw-backs of utilizing wound fluids to assess wound progression in terms of proteolytic activity.