rhVEGF and Experimental Rat Skin Flaps: Systemic or Local Administration and Morphological Characteristics

Abstract

Skin flap survival is a significant problem in skin surgery; in particular, inadequate arterial or venous blood supply results in necrosis of the distalmost portion. The aim of this study was to evaluate the ability of Vascular Endothelial Growth Factor (VEGF) of modifying the morphological features of skin flaps. Bilateral epigastric skin flaps were raised in 16 Wistar male rats. The epigastric artery and vein of the left flaps were clamped and then injected with rhVEGF (8 rats) or saline (8 rats). The right flaps were not clamped and received rhVEGF or saline systemically. The rats were euthanized on the seventh day and flap skin samples collected. Tissue fragments were subject to immunohistochemical (rhVEGF, VEGFr, VIII factor, CD34 antibodies), ultrastructural and morphostructural investigations. The results showed that rhVEGF improved the condition of flaps and that systemic administration was effective in promoting the development of an adequate vascular network.

Effects of Vascular Endothelial Growth Factor on Survival of Surgical Flaps: A Review of Experimental Studies

“…35 Besides intra-arterial injection, local and systemic administrations of VEGF are also effective in increasing the vascularity of epigastric rat skin flaps. 103 VEGF-modulated increases in capillary permeability result in an increase in extravascular tissue fluid. 104 In fluid released by VEGF, simultaneous suppression of inflammatory cytokines may create a sustaining transudate compatible with the concept of serum inhibition as a nutritive medium for ischemic tissue.…”

Local Transplant of Human Umbilical Cord Matrix Stem Cells Improves Skin Flap Survival in a Mouse Model

“…The neovascularization of the skin flap is a complex process that involves the proliferation of endothelial cells and cooperation among various growth factors (Tucci et al 2001;Zhang et al 2001). The steps between mesenchymal stem cell application and neovascularization remain unclear, but experimental studies have shown that BM MSCs and ADSCs can promote angiogenesis through promoting the release of growth factors (Uysal et al 2010;Ding et al 2011).…”

“…The steps between mesenchymal stem cell application and neovascularization remain unclear, but experimental studies have shown that BM MSCs and ADSCs can promote angiogenesis through promoting the release of growth factors (Uysal et al 2010;Ding et al 2011). Among them, VEGF and bFGF have been proved to be the important growth factors in promoting angiogenesis of skin flaps in various animal models (Padubidri et al 1996;Tucci et al 2001;Zhang et al 2001). In the complex neovascularization cascade, VEGF is thought to be the main controller, with a positive feedback control exerted by endothelial cells (Murohara et al 1998;Taub et al 2000).…”

Growth factors and flap survival

“…31,32 Many studies were conducted on the use of VEGF to induce therapeutic angiogenesis in improving flap survival. Padubidri and Browne 33 and Tucci et al 34 first used VEGF in augmentation of angiogensis in a rat epigastric skin flap model. Results showed that the mean percentage of surviving flap area in VEGF-treated flaps was significantly higher than that of controls without treatment.…”

“…Additional research on growth factors in flap survival obtained similar results with either systemic or local intratissue injection. 12,26,29,30,34,35,42,44 Applications of growth factors by routes of topical administration and immersed in gelfoam were also reported. 14À16,24,41 Intra-arterial administrations of growth factors were also demonstrated to improve the pedicled skin and muscle flap survival.…”