title: Platelet-derived growth factor B, but not fibroblast growth factor 2, plasmid DNA improves survival of ischemic myocutaneous flaps.
abstract: OBJECTIVE
  Tissue flaps are commonly used for surgical reconstruction, especially to cover difficult wounds and in breast reconstruction following mastectomy. Complications due to inadequate flap perfusion are a source of morbidity and, in the lower extremity, can result in amputation.
  
  
  METHODS
  Laboratory.
  
  
  METHODS
  We evaluated the ability of platelet-derived growth factor (PDGF) B and fibroblast growth factor 2 plasmid DNA, formulated in a type I collagen matrix, to promote tissue survival in a rat transverse rectus abdominis muscle flap model based on the inferior deep epigastric vascular supply. In the absence of any therapeutic agent, only about 24% of flap tissue survives in this model. The DNA/matrix formulations were delivered subcutaneously into the skin paddles 7 days before flap elevation, and tissues were harvested 7 days later.
  
  
  RESULTS
  Our studies reveal dramatic increases in overall vascularity after treatment with PDGF-B and fibroblast growth factor 2 plasmid DNA; however, only PDGF-B increased flap survival (130% increase at 228 micro g/cm(2) of plasmid DNA vs controls; P<.01). Transdermal spectral imaging demonstrated an increase in patent vessels supporting blood flow in flaps treated with PDGF-B plasmid DNA vs the fibroblast growth factor 2 transgene.
  
  
  CONCLUSIONS
  Matrix-enabled gene therapy may provide an effective nonsurgical approach for promoting flap survival and is well suited for surgical applications in which transient therapeutic transgene expression is desired.
authors.affiliation: Wound Healing Research Laboratory, the Division of Plastic and Reconstructive Surgery, Northwestern University, Chicago, IL, USA.
authors.forename: John
authors.initials: J
authors.lastname: Hijjawi
authors.forename: Jon E
authors.initials: JE
authors.lastname: Mogford
authors.forename: Lois A
authors.initials: LA
authors.lastname: Chandler
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Cross
authors.forename: Hakim
authors.initials: H
authors.lastname: Said
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Sosnowski
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Mustoe
mesh_terms: D000818:Animals; D004247:DNA; D004195:Disease Models, Animal; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006084:Graft Rejection; D006085:Graft Survival; D007150:Immunohistochemistry; D007511:Ischemia / Q000517:prevention & control*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D010957:Plasmids / Q000494:pharmacology*; D011336:Probability; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017568:Rectus Abdominis / Q000473:pathology / Q000601:surgery; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013524:Surgical Flaps / Q000098:blood supply*
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D016222:Fibroblast Growth Factor 2; D004247:DNA