Vascular Endothelial Growth Factor Gene Therapy in Improvement of Skin Paddle Survival in a Rat TRAM Flap Model

Abstract

The use of growth factors in inducing angiogenesis and enhancing flap viability has provided promising results. Targeted gene therapy has evolved in hopes of increasing the longevity and effectiveness of these growth factor treatments. The purpose of this study was to examine the effect of preoperative treatment by vascular endothelial growth factor (VEGF) plasmid DNA on the survival of the skin paddle in a rat pedicled TRAM flap model. In part one of the study, VEGF plasmid DNA incorporated with lipofectamine was injected into the subcutaneous fascial layer of the upper abdominal walls of the rats. At 4 days postoperatively, biopsies were taken from the injected area for histology and VEGF protein quantification. In part two of the study, the rats were divided into three groups. In one experimental group, the VEGF plasmid DNA was injected into the subcutaneous fascial layer in the area where the TRAM flap would be elevated. In two control groups, the plasmid without VEGF DNA and saline were injected. The flaps were raised and replaced 4 days after injection. Flap survival was examined. Results showed that tissue receiving VEGF plasmid DNA injection revealed new vessel sprouting. The VEGF levels in these tissues were significantly higher than in the tissue not receiving VEGF plasmid DNA. In flap survival, the mean viable area of the skin paddles receiving preoperative VEGF plasmid DNA injection was significantly larger than that of flaps receiving no VEGF plasmid DNA and saline injection. This study demonstrated that preoperative subcutaneous injection of VEGF plasmid DNA could induce angiogenesis and improve TRAM skin paddle survival.