Biofilms are of great importance in infection control and healthcare-associated infections (HCAI) due to their inherent tolerance and 'resistance' to antimicrobial therapies. Biofilms have been shown to develop on medical device surfaces and dispersal of single and clustered cells imply a significant risk of microbial dissemination within the host and increased risk of infection. Although routine microbiological testing assists with the diagnosis of a clinical infection, there is no 'gold standard' available to reveal the presence of microbial biofilm from samples collected within clinical settings. Furthermore, such limiting factors as viable but non-culturable (VBNC) microorganisms and small colony variants (SCVs) often prevent a successful detection. In order to increase the chances of detection and provide a more accurate diagnosis, a combination of microbiological culture techniques and molecular methods should be employed. Measures such as antimicrobial coating and surface alterations of medical devices provide promising opportunities in the prevention of biofilm formation on medical devices.

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.

Significance: Chronic wounds become caught in a state of inflammation causing an increase in levels of degrading proteases, which destroy components of the extracellular matrix (ECM) that are essential for the wound healing process. This review aims to highlight and provide readers with an overview of what is currently known about the role of pH and its effect on the ECM and biofilms within healing and nonhealing wounds. Recent Advances: The pH profiles of healthy skin, acute wounds, and chronic wounds differ significantly. Chronic wounds have an alkaline pH whereas healthy skin has a slightly acidic pH. Although there is evidence on the effect of pH on protease production and bacterial proliferation in wounds, there is little evidence to show its effect on ECM synthesis and degradation. Critical Issues: The implications for the complex nature of chronic wounds are that no single treatment is relevant for all wounds, but rather a combination of methodologies must be adopted. It is known that pH of a wound reduces throughout the stages of healing, suggesting that wound pH measurements could be beneficial to identify nonhealing wounds earlier and decide on the most appropriate course of treatment. Future Direction: Wound healing is a very complex process with multiple factors known to play a role. All aspects of the nonhealing wound (defective ECM, pH, microbial invasion, and excess proteases) need to be taken into account when investigating or clinically treating a chronic wound.