Platelet-derived growth factor B, but not fibroblast growth factor 2, plasmid DNA improves survival of ischemic myocutaneous flaps

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 mug/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. 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.