Vascular endothelial growth factor (VEGF) gene transfer enhances surgical revascularization of necrotic bone

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Abstract
Avascular necrosis of bone is a relatively common clinical condition caused by inflammatory conditions, steroid or other drug use, and trauma that affect many different sites in man. Revascularization of the necrotic bone is slow to occur, often resulting in bone resorption and eventual collapse of the involved bone. Rapid revascularization and subsequent bone remodeling may lead to improved outcomes. Surgical revascularization with arterovenous bundles (AV bundles) or vascularized bone grafts results in neoangiogenesis and bone remodeling. Gene transfer of an angiogenic factor to the vessel wall may be an additional strategy to further accelerate this process. In this study, we examined the effectiveness of vascular endothelial growth factor (VEGF) gene transfer to augment surgical revascularization of necrotic bone. An adenoviral vector, either with the VEGF gene (VEGF-A) or identical virus without the cDNA VEGF insert (ADV-DeltaE1) was used to transduce endothelial cells in rabbit saphenous arteries. The artery was then placed with its venae comitantes as an AV bundle into necrotic iliac crest bone in vivo. Angiogenesis in the necrotic bone was quantified by bone blood flow measurement and assessment of vessel density following microangiography. The extent of neoangiogenesis was significantly greater in the VEGF group than the control group at 1 week postoperatively.