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John Hijjawi, MD; Jon E. Mogford, PhD; Lois A. Chandler, PhD; Kevin J. Cross, MD; Hakim Said, MD; Barbara A. Sosnowski, PhD; Thomas A. Mustoe, MD

Arch Surg. 2004;139:142-147.

Hypothesis  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.

Setting  Laboratory.

Interventions  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 µg/cm² 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.

Conclusion  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.

From the Wound Healing Research Laboratory, the Division of Plastic and Reconstructive Surgery, Northwestern University, Chicago, Ill (Drs Hijjawi, Mogford, Cross, Said, and Mustoe); and Selective Genetics, Inc, San Diego, Calif (Drs Chandler and Sosnowski).

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