title: Elevated levels of matrix metalloproteinases and chronic wound healing: an updated review of clinical evidence.
abstract: OBJECTIVE
  In the past 20 years, research and clinical trials on the healing process of chronic wounds have highlighted the key role of the family of enzymes called matrix metalloproteinases (MMPs). If a strong correlation between the course of healing of chronic wounds and the levels of a biological marker can be demonstrated, then it may be possible to: i) identify the best marker threshold to predict the clinical evolution of the pathology; and ii) if causality has been found between the marker and pathology, to improve the healing outcome, to change the marker level.
  
  
  METHODS
  The databases Medline and Embase were searched to identify clinical trials pertaining to the assessment of MMPs in chronic wounds with the following keywords 'metalloproteinase' or 'metalloprotease' and 'wound healing'. Clinical trials were considered for inclusion if they enrolled patients with cutaneous chronic wounds and were published in English. More than 50 clinical trials, consensus documents and guidelines were assessed for this review.
  
  
  RESULTS
  MMPs play key roles in the wound healing process, and excessive expression and activation of some of these enzymes is seen in chronic cutaneous wounds where healing is delayed. Levels of MMPs are affected by a number of factors, including patient and wound characteristics.
  
  
  CONCLUSIONS
  Levels of MMPs can be used to indicate the prognosis of chronic wounds and protease modulating treatments used to improve healing rates.
  
  
  BACKGROUND
  The authors report no conflicts of interest in this work.
authors.affiliation: University Podiatry Clinic, College of Medicine, Complutense University, Madrid, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Lazaro
authors.affiliation: Department of Systems Medicine - University of Tor Vergata - Roma, Italia.
authors.forename: V
authors.initials: V
authors.lastname: Izzo
authors.affiliation: Rothschild University Hospital, APHP, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Meaume
authors.affiliation: Department of Surgery and Cancer, Faculty of Medicine, Imperial College School of Medicine, Charing Cross Hospital, London, UK.
authors.forename: A H
authors.initials: AH
authors.lastname: Davies
authors.affiliation: Department of Endocrinology, Diabetology and Geriatrics - Klinikum Bürgerhospital, Stuttgart, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Lobmann
authors.affiliation: Department of Systems Medicine - University of Tor Vergata - Roma, Italia.
authors.forename: L
authors.initials: L
authors.lastname: Uccioli
mesh_terms: D000208:Acute Disease; D002908:Chronic Disease; D006801:Humans; D007206:Individuality; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D011379:Prognosis; D014945:Wound Healing; D014947:Wounds and Injuries / Q000201:enzymology*
chemical_list: D020782:Matrix Metalloproteinases
keywords: chronic wound; matrix metalloproteinase; wound healing