Matrix metalloproteinase inhibition and antibioticsin the treatment of chronic wounds

Abstract

The burden of chronic wounds to patients and the challenge they present to health care workers is enormous. Acute wounds heal in an orderly manner by coagulation, followed by an inflammatory phase with re-formation of the extracellular matrix, cell proliferation and finally remodelling with scar formation. In chronic wounds one or more of these stages becomes unregulated with the major difference appearing to be the destruction of the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) and increased inflammatory activity which is frequently caused by infection. The important targets appear to be the MMPs which can be inhibited by both endogenous and synthesised inhibitors which have been shown to reduce MMP activity. Interestingly, doxycycline and tetracyclines have recently been shown to also inhibit MMP activity. In vitro, these also appear to have the ability to disrupt bacterial biofilms which are often present in chronic wounds. However, although the efficacy of these antibiotics has been demonstrated in periodontal disease, studies are needed to test their efficacy in chronic wounds.