Approaches to Control and Monitor Protease Levels in Chronic Wounds

Abstract

Some wounds do not follow the typical healing trajectory and show very little, if any, progress. They dreadfully threaten the patients' quality of life and may even lead to limb amputation and death. Several interrelated systemic and local factors may cause a delay in wound healing. The microenvironment of these wounds can be different from wounds that heal spontaneously or with standard treatment. As discussed in the present work, proteases’ levels or activity can be elevated in some cases of chronic ulcers; infection can aggravate the situation. A detailed overview of the proteases’ effect on wound healing is presented in this work. Assuming untimely or irregularly excessive proteolytic activity plays a pathological role, some researchers targeted attenuation of protease level as a strategy to promote healing. This can be done via different approaches, including physical removal, inhibiting their activity, and controlling their expression directly through gene silencing or indirectly, for instance, by resolving infection. Apart from targeting protease modulation as a therapeutic strategy, many studies have examined the protease state to gain insights into the underlying mechanisms by which a remedy, dressing, or specific therapy has affected the healing process. This study aims to provide an overview of the studies in these two categories. Of course, various proteases are involved in the healing process, but in each study, usually, only one or some of them are investigated; matrix metalloproteinase-2 (MMP-2), MMP-9, and human neutrophil elastase (HNE) are among them. Furthermore, in some cases, cumulative proteolytic activity is evaluated in terms of gelatinolytic, collagenolytic, or caseinolytic activity, which is also absolutely beneficial. Some research groups have considered the potential of proteases as a diagnostic or prognostic biomarker and have tried to develop some sensors or indicators; this topic is also covered in the present work.