Comparison of the effectiveness of gene therapy with transforming growth factor-β or extracorporal shock wave therapy to reduce ischemic necrosis in an epigastric skin flap model in rats

The induction of neoangiogenesis by exogenous growth factors in failing skin flaps has recently yielded promising results. Gene transfer with virus vectors has been introduced as a highly capable route of administration for growth factors, such as vascular endothelial growth factor or fibroblast growth factor. Extracorporal shock waves (ESW) deliver energy by means of high amplitudes of sound to the target tissue and have been shown to induce angiogenesis. We compared the effectiveness of gene therapy with adenovirus-mediated transforming growth factor-beta (TGF-beta) and ESW therapy to treat ischemically challenged epigastric skin flaps in a rat model. Thirty male Sprague-Dawley rats were divided into three groups of 10 each with an 8 x 8 cm epigastric skin flap. Rats received either subdermal injections of adenovirus (Ad) encoding TGF-beta (10(8) pfu) or ESW treatment with 750 impulses at 0.15 mJ/mm(2). The third group received no treatment and served as a control group. Flap viability was evaluated after 7 days and digital images of the epigastric flaps were taken and areas of necrotic zones relative to total flap surface area calculated. Histologic evaluation and increased angiogenesis were confirmed by CD31 immunohistochemistry. Overall, there was a significant increase in mean percent surviving area in the Ad-TGF-beta group and the ESW group compared to the control group (ESW group: 97.7 +/- 1.8% vs. Ad-TGF-beta: 90.3 +/- 4.0% and control group: 82.6 +/- 4.3%; p < 0.05). Furthermore, in the ESW group mean percent surviving areas were significantly larger than in the Ad-TGF-beta group (ESW group: 97.7 +/- 1.8% vs. Ad-TGF-beta: 90.3 +/- 4.0%; p < 0.05). Flap vascularization was increased by Ad-TGF-beta and ESW with numerous vessels, however, there was no significant difference between the two treatment groups. We conclude that treatment with ESW enhances epigastric skin flap survival significantly more than Ad-TGF-beta treatment and thus represents a modality that is feasible, cost-effective, and less invasive compared to gene therapy with growth factors to improve blood supply to ischemic tissue.