Accelerated Flap Prefabrication with Vascular Endothelial Growth Factor

Abstract

Vascular endothelial growth factor (VEGF) is a potent promoter of angiogenesis that has been shown to enhance revascularization of ischemic tissues, including skin flaps. This study was designed to investigate the value of a single topical application of recombinant human VEGF to accelerate flap viability in a rat model of a non-ischemic prefabricated flap. Prefabricated flaps were created in 48 Sprague-Dawley rats. An autologous tail artery loop was anastomosed to the femoral artery and vein, and implanted subcutaneously in the lower abdomen. Flaps were divided into two groups of 24 each. At the time of loop implantation the control group received 0.9 percent NaCl or a 16 percent vol/wet polyvinyl alcohol (PVA) solution: the treatment group received VEGF in 0.9 percent NaCl or VEGF in PVA. The PVA gel was used to facilitate topical application In each group, 3- x 4-cm flaps nurtured by the tail artery pedicle were elevated and resutured into place after 3, 4, and 5 weeks. The percentage of surviving skin of each flap was determined by planimetry 7 days after flap elevation. Mean skin survival areas at 3, 4, and 5 weeks were control group 0 percent. 8 percent and 17.5 percent; and VEGIF-treated group, 6 percent, 40 percent, and 66.7 percent respectively VEGF significantly improved flap survival by 5 weeks (p = 0.02). These results suggest that VEGF can accelerate maturation of prefabricated flaps. This approach could expand the application of flap prefabrication as a resource for reconstructive surgery.

The Notch pathway is a critical regulator of angiogenesis in a skin model of ischemia

“…VEGF serves as the primary initiator of angiogenic sprouting. [25][26][27] Coincidentally, with initiating angiogenesis, VEGF also upregulated DLL4 expression within the endothelium of angiogenic vessels. Activated Notch acts in feedback fashion as a 'brake' or negative regulator of VEGF-induced angiogenesis, modulating this process to control over exuberant vascular sprouting, thereby promoting the timely formation of a productive and well-differentiated vascular network.…”

Transplantation of Adipose-Derived Stem Cells Promotes Formation of Prefabricated Flap in a Rat Model

“…In order to prevent complications like this, several studies have been done to achieve better neovascularization during flap prefabricating process, such as the application of angiogenic cytokines vascular endothelial growth factor (VEGF) (Li et al 2000), basic fibroblast growth factor (bFGF) (Bayati et al 1998), and transforming growth factor (TGF)-β (Iwasawa 1993), or the administration of gene therapy (Lubiatowski et al 2002). However, neither the local application of angiogenic cytokines nor the administration of gene therapy can be effective long-term without obvious side effects.…”

Improved survival of rat ischemic cutaneous and musculocutaneous flaps after VEGF gene transfer

“…5), confirming a property already described in literature. 6,13,14,22,39,40 Immunostaining the same samples with an antibody specific for a-Smooth Muscle Actin, emphasized the neoangiogenetic process taking place in AAV-VEGF-treated tissues, by demonstrating the massive presence of arterial vessels (Fig. 6), particularly in samples from group 9 (vector inoculation 14 days before surgery).…”