title: Human beta-defensin-3 promotes wound healing in infected diabetic wounds.
abstract: BACKGROUND
  Infected wounds present a major complication in patients with diabetes. Staphylococcus aureus is the most common single isolate in diabetic wounds. Human beta-defensin (hBD)-3 is antimicrobial active and appears to play a key role in the immune response. The present study aimed to analyse the effect of hBD-3 expression in a model of infected diabetic wounds.
  
  
  METHODS
  Excisional wounds were created on the backs of Yorkshire pigs and Ad5-CMV-hBD-3 vectors were microseeded. Wounds were inoculated with S. aureus, covered with a polyurethane chamber and analysed for transgene expression, bacterial infection, re-epithelialization, wound contraction, wound fluid production and blood vessel formation.
  
  
  RESULTS
  hBD-3-treated wounds showed a total bacterial load of 2.1 x 10(8) colony-forming units (CFU)/g tissue, versus 1.3 x 10(9) CFU/g tissue for controls (p < 0.001) at day 4. At day 12, no statistical difference could be detected. Re-epithelialization showed 75 +/- 15% wound closure for hBD-3 expressing wounds and 50 +/- 16% for controls (p < 0.01). hBD-3 expression was in the range 15-20 ng/ml of wound fluid during day 1-4. The lower dose of 2 x 10(9) Ad5-CMV-hBD-3 showed no effect, suggesting a dose dependency for hBD-3.
  
  
  CONCLUSIONS
  In the present study, we show that hBD-3 expression significantly promotes wound closure in S. aureus infected diabetic wounds in a preclinical large-animal model. Furthermore, a ten-fold reduction of bacterial growth on day 4 was detected. These findings indicate that beta-defensin-3 may play a major role in diabetic wound healing and wound infections.
authors.affiliation: Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hirsch
authors.forename: Malte
authors.initials: M
authors.lastname: Spielmann
authors.forename: Baraa
authors.initials: B
authors.lastname: Zuhaili
authors.forename: Magdalena
authors.initials: M
authors.lastname: Fossum
authors.forename: Marie
authors.initials: M
authors.lastname: Metzig
authors.forename: Till
authors.initials: T
authors.lastname: Koehler
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Steinau
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.forename: Andrew Bruce
authors.initials: AB
authors.lastname: Onderdonk
authors.forename: Lars
authors.initials: L
authors.lastname: Steinstraesser
authors.forename: Elof
authors.initials: E
authors.lastname: Eriksson
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D048909:Diabetes Complications / Q000503:physiopathology / Q000628:therapy*; D003920:Diabetes Mellitus; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D018919:Neovascularization, Physiologic; D013207:Staphylococcal Skin Infections / Q000382:microbiology / Q000503:physiopathology / Q000628:therapy*; D013211:Staphylococcus aureus / Q000378:metabolism; D013552:Swine; D019076:Transgenes; D014945:Wound Healing; D014946:Wound Infection / Q000382:microbiology / Q000503:physiopathology* / Q000628:therapy*; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism
chemical_list: C422950:DEFB103A protein, human; D023083:beta-Defensins