23.2 VEGF enhances angiogenic response in experimental wounds as measured by tensile properties of the wound, increased epithelialization, and decreased time to closure          

Hyacinth Entero; Arber Kodra; Vincent Wang, PhD; Michael Golinko, MD; Marjana Tomic, PhD; Paul Ehrlich, PhD; Harold Brem, MD, Columbia University Medical Center

Vascular endothelial growth factor (VEGF) is a local stimulator of angiogenesis. In this study, we hypothesized that local sustained release of VEGF using adenoviral vector mediated gene transfer could reverse the reduced angiogenic response observed in diabetic wounds and accelerate wound healing. This hypothesis was tested by determining the specific effects of VEGF165 application on components of the wound healing process: epithelialization, skin biomechanical properties, histology, and time to 100% wound closure. To determine the effects of VEGF on wound healing in vivo, ADV/VEGF165 and controls (vehicle and saline) were injected into excisional and incisional wounds created on dorsum of BKS.Cg-m+/+Leprdb and NOD mice and mechanical properties and histological evaluations were performed 10, 14, or 21 days post injury. Wounds treated with ADV/VEGF165, healed 6.6 days faster than controls. Treated wounds healed in 27.25 ± 1.4 days. Saline treated wounds healed in 34.2 ± 7.0 days, while wounds administered with vehicle control alone healed in 33.5 ± 6.5 days. Additionally, analysis of stiffness (N/mm) indicated that skin excised from wound sites of animals treated with VEGF165 had a stronger wound breaking strength than skin excised from control animals' wound sites. Furthermore, histological analysis revealed accelerated epithelialization at wound sites treated with VEGF165 as measured by analysis of the thickness of the epithelial layer. These results suggest that VEGF accelerates closure of wounds and provide evidence for a new mechanism to increase epithelialization at wound sites.