title: Angiogenesis in wounds treated by microdeformational wound therapy.
abstract: BACKGROUND
  Mechanical forces play an important role in tissue neovascularization and are a constituent part of modern wound therapies. The mechanisms by which vacuum assisted closure (VAC) modulates wound angiogenesis are still largely unknown.
  
  
  OBJECTIVE
  To investigate how VAC treatment affects wound hypoxia and related profiles of angiogenic factors as well as to identify the anatomical characteristics of the resultant, newly formed vessels.
  
  
  METHODS
  Wound neovascularization was evaluated by morphometric analysis of CD31-stained wound cross-sections as well as by corrosion casting analysis. Wound hypoxia and mRNA expression of HIF-1α and associated angiogenic factors were evaluated by pimonidazole hydrochloride staining and quantitative reverse transcription-polymerase chain reaction (RT-PCR), respectively. Vascular endothelial growth factor (VEGF) protein levels were determined by western blot analysis.
  
  
  RESULTS
  VAC-treated wounds were characterized by the formation of elongated vessels aligned in parallel and consistent with physiological function, compared to occlusive dressing control wounds that showed formation of tortuous, disoriented vessels. Moreover, VAC-treated wounds displayed a well-oxygenated wound bed, with hypoxia limited to the direct proximity of the VAC-foam interface, where higher VEGF levels were found. By contrast, occlusive dressing control wounds showed generalized hypoxia, with associated accumulation of HIF-1α and related angiogenic factors.
  
  
  CONCLUSIONS
  The combination of established gradients of hypoxia and VEGF expression along with mechanical forces exerted by VAC therapy was associated with the formation of more physiological blood vessels compared to occlusive dressing control wounds. These morphological changes are likely a necessary condition for better wound healing.
authors.affiliation: Tissue Engineering and Wound Healing Laboratory, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA. erbapaolo@hotmail.com
authors.forename: Paolo
authors.initials: P
authors.lastname: Erba
authors.forename: Rei
authors.initials: R
authors.lastname: Ogawa
authors.forename: Maximilian
authors.initials: M
authors.lastname: Ackermann
authors.forename: Avner
authors.initials: A
authors.lastname: Adini
authors.forename: Lino F
authors.initials: LF
authors.lastname: Miele
authors.forename: Pouya
authors.initials: P
authors.lastname: Dastouri
authors.forename: Doug
authors.initials: D
authors.lastname: Helm
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Mentzer
authors.forename: Robert J
authors.initials: RJ
authors.lastname: D'Amato
authors.forename: George F
authors.initials: GF
authors.lastname: Murphy
authors.forename: Moritz A
authors.initials: MA
authors.lastname: Konerding
authors.forename: Dennis P
authors.initials: DP
authors.lastname: Orgill
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D006097:Granulation Tissue / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000473:pathology; D054843:Negative-Pressure Wound Therapy; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009779:Occlusive Dressings; D010100:Oxygen / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000098:blood supply / Q000293:injuries* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen