Platelet-derived growth factor B, but not fibroblast growth factor 2, plasmid DNA improves survival of ischemic myocutaneous flaps.
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.
Hijjawi
John
J
Wound Healing Research Laboratory, the Division of Plastic and Reconstructive Surgery, Northwestern University, Chicago, IL, USA.
Mogford
Jon E
JE
Chandler
Lois A
LA
Cross
Kevin J
KJ
Said
Hakim
H
Sosnowski
Barbara A
BA
Mustoe
Thomas A
TA
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*
D020574:Proto-Oncogene Proteins c-sis; D016222:Fibroblast Growth Factor 2; D004247:DNA