title: Noncontact, low-frequency ultrasound therapy enhances neovascularization and wound healing in diabetic mice.
abstract: BACKGROUND
  Chronic wounds are a major source of morbidity for patients and represent a significant health burden. Implementing noninvasive techniques that accelerate healing of these wounds would provide great benefit. Ultrasound appears to be an effective modality for the treatment of chronic wounds in humans. MIST Therapy is a noncontact, low-frequency ultrasound treatment delivered through a saline mist. A variety of mechanisms have been proposed to explain the efficacy of ultrasound therapy, but the underlying molecular and cellular pathways impacted by this technique remain unclear. The in vivo effect of noncontact, low-frequency ultrasound was therefore examined in a humanized excisional wound model.
  
  
  METHODS
  The treatment group received noncontact, low-frequency ultrasound therapy three times per week, whereas the control group received a standard dressing change. Wounds were photographed at regular intervals to calculate healing kinetics. Wound tissue was harvested and processed for histology, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The MIST group demonstrated significantly accelerated wound healing, with 17.3 days to wound closure compared with 24 days in the controls (p < 0.05). This improvement became evident by day 9, with healing evidenced by significantly decreased mean wound area relative to original size (68 percent versus 80 percent; p < 0.01). Expression of markers of neovascularization (stromal cell-derived factor 1, vascular endothelial growth factor, and CD31) was also increased in the wound beds of noncontact, low-frequency ultrasound-treated mice compared with controls.
  
  
  CONCLUSIONS
  Noncontact, low-frequency ultrasound treatment improves neovascularization and wound closure rates in excisional wounds for diabetic mice, likely because of the stimulated release of angiogenic factors.
authors.affiliation: Stanford, Calif. From the Department of Surgery, Stanford University School of Medicine.
authors.forename: Zeshaan N
authors.initials: ZN
authors.lastname: Maan
authors.forename: Michael
authors.initials: M
authors.lastname: Januszyk
authors.forename: Robert C
authors.initials: RC
authors.lastname: Rennert
authors.forename: Dominik
authors.initials: D
authors.lastname: Duscher
authors.forename: Melanie
authors.initials: M
authors.lastname: Rodrigues
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Natalie
authors.initials: N
authors.lastname: Ho
authors.forename: Arnetha
authors.initials: A
authors.lastname: Whitmore
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hu
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Gurtner
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000098:blood supply* / Q000293:injuries / Q000378:metabolism; D016896:Treatment Outcome; D014464:Ultrasonic Therapy / Q000379:methods*; D014945:Wound Healing / Q000502:physiology
chemical_list: D015415:Biomarkers