title: Mechanisms of action of external volume expansion devices.
abstract: BACKGROUND
  External volume expansion by suction has been proposed to improve the survival of fat grafting by preparing the recipient site. In previous experimental work, external volume expansion demonstrated the capacity to stimulate cell proliferation, vessel remodeling, and adipogenesis. This study investigated possible mechanisms underlying these observed changes.
  
  
  METHODS
  A miniaturized external volume expansion device was applied to the dorsum of mice for 2 hours. Hypoxia during stimulation was assessed with pimonidazole hydrochloride, and tissue perfusion was measured for up to 2 days using hyperspectral imaging. Treated tissues were evaluated by microscopy for edema, inflammation, and the effects on cell proliferation and vessel remodeling.
  
  
  RESULTS
  External volume expansion-treated tissues were grossly expanded with 2 hours of stimulation, developing a macroscopic swelling that regressed slowly over the course of hours following stimulus cessation. This gross swelling was reflective of histologic signs of intense edema, persistent for at least 1 hour after external volume expansion. Tissues were hypoxic during stimulation, and hyperspectral imaging demonstrated decreased tissue content of both oxygenated and deoxygenated hemoglobin in the first hour after external volume expansion release. The onset of inflammation was already apparent by the end of stimulation and remained elevated through 2 days after external volume expansion. At this time point, epidermal and dermal cell proliferation and vascular density were significantly increased.
  
  
  CONCLUSIONS
  External volume expansion sets in motion various mechanisms, including mechanical stimulation, edema, ischemia, and inflammation, that over distinct time periods maintain an environment conducive to cell proliferation and angiogenesis, which can be elicited even by a single 2-hour external volume expansion cycle.
authors.affiliation: Boston and Worcester, Mass.; and Padova, Italy From the Tissue Engineering and Wound Healing Laboratory, Division of Plastic Surgery, Brigham and Women's Hospital and Harvard Medical School; the Institute of Plastic, Reconstructive and Aesthetic Surgery, University of Padova; the Division of Plastic Surgery, University of Massachusetts Medical School; and Back Bay Plastic Surgery.
authors.forename: Luca
authors.initials: L
authors.lastname: Lancerotto
authors.forename: Michael S
authors.initials: MS
authors.lastname: Chin
authors.forename: Brian
authors.initials: B
authors.lastname: Freniere
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Lujan-Hernandez
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.forename: Alessandro Valderrama
authors.initials: AV
authors.lastname: Vasquez
authors.forename: Franco
authors.initials: F
authors.lastname: Bassetto
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Del Vecchio
authors.forename: Janice F
authors.initials: JF
authors.lastname: Lalikos
authors.forename: Dennis P
authors.initials: DP
authors.lastname: Orgill
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D020405:Dermis / Q000098:blood supply / Q000473:pathology / Q000502:physiology; D004487:Edema / Q000175:diagnosis / Q000209:etiology; D004817:Epidermis / Q000473:pathology / Q000502:physiology; D000860:Hypoxia / Q000175:diagnosis / Q000209:etiology; D007150:Immunohistochemistry; D007249:Inflammation / Q000175:diagnosis / Q000209:etiology; D016014:Linear Models; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic; D061848:Optical Imaging; D015626:Tissue Expansion / Q000009:adverse effects / Q000295:instrumentation* / Q000379:methods; D015625:Tissue Expansion Devices / Q000009:adverse effects