title: Systematic review of molecular mechanism of action of negative-pressure wound therapy.
abstract: BACKGROUND
  Negative-pressure wound therapy (NPWT) promotes angiogenesis and granulation, in part by strain-induced production of growth factors and cytokines. As their expression profiles are being unravelled, it is pertinent to consider the mode of action of NPWT at the molecular level.
  
  
  METHODS
  MEDLINE (January 1997 to present), Embase (January 1997 to present), PubMed (no time limit), the Cochrane Database of Systematic Reviews and the Cochrane Controlled Trials Register were searched for articles that evaluated the influence of NPWT on growth factor expression quantitatively.
  
  
  RESULTS
  Sixteen studies met the inclusion criteria. Tumour necrosis factor expression was reduced in acute and chronic wounds, whereas expression of interleukin (IL) 1β was reduced in acute wounds only. Systemic IL-10 and local IL-8 expression were increased by NPWT. Expression of vascular endothelial growth factor, fibroblast growth factor 2, transforming growth factor β and platelet-derived growth factor was increased, consistent with mechanoreceptor and chemoreceptor transduction in response to stress and hypoxia. Matrix metalloproteinase-1, -2, -9 and -13 expression was reduced but there was no effect on their enzymatic inhibitor, tissue inhibitor of metalloproteinase 1.
  
  
  CONCLUSIONS
  Cytokine and growth factor expression profiles under NPWT suggest that promotion of wound healing occurs by modulation of cytokines to an anti-inflammatory profile, and mechanoreceptor and chemoreceptor-mediated cell signalling, culminating in angiogenesis, extracellular matrix remodelling and deposition of granulation tissue. This provides a molecular basis for understanding NPWT.
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, London, UK; Departments of  Plastic Surgery, Royal Free Hospital, London, UK.
authors.forename: G E
authors.initials: GE
authors.lastname: Glass
authors.forename: G F
authors.initials: GF
authors.lastname: Murphy
authors.forename: A
authors.initials: A
authors.lastname: Esmaeili
authors.forename: L-M
authors.initials: LM
authors.lastname: Lai
authors.forename: J
authors.initials: J
authors.lastname: Nanchahal
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D054843:Negative-Pressure Wound Therapy; D051381:Rats; D013552:Swine; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000503:physiopathology / Q000628:therapy*
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D020782:Matrix Metalloproteinases