Effects of vascular endothelial growth factor on diabetic wound healing: An experimental study in mice

Effects of Vascular Endothelial Growth Factor on Diabetic Wound Healing ABSTRACT Diabetes mellitus has become an important issue in healthcare world wide. Diabetic patients often suffer from chronic wounds. Long lasting wound leads not only to health problems but also, to a burden in social and psychological settings. With this respect, research for treatment of chronic diabetic wounds is of great importance. The aim of the study is, to assess the effects of vascular endothelial growth factor, released from calcium alginate microspheres, in a controlled release system, on wound angiogenesis and epithelization in mice diabetic wound model. Mice were grouped in four sets. 3 groups were given 200 mg/ kg streptozocin. Diabetic state was confirmed before the surgical intervention. Mice having blood glucose level lower than 300mg/dl was excluded from the study. Microvascular complications of diabetes were assumed to settle within 6 weeks after the injection. Excisional wounds were created in dorsal area of the mice. Following wounding procedure, DM+VEGF group was given 1 [Ag VEGF in calcium alginate controlled release system. DM+Alginate group was given sham microspeheres prepared with % 0,9 NaCl. One diabetic and one normal groups were devoid of any intervention. Groups were divided into further subsets for histopathology and photographic examination. H&E sections were evaluated for acute and chronic inflammation and microvascular density. Immunhistochemistry staining for VEGF165 was made for evaluation of neovascularisation. Wound area was measured in 3 days intervals. Percent and cm2 wound area was assesed with respect to time. Results were examined using ANOVA analysis. Fastest wound closure was seen in normal group. On 1501 day, when all normal wounds were epithelized, DM+VEGF group had 81,77 %, DM group 70,78 % epithelization. The differrence was statistically significant. Mean microvascular density of groups were, DM+VEGF group 17,97 ± 2,14, DM+Alginate group 6,6 ± 0,83, DM group 4,22 ± 1,03, normal group 7,21 ± 1,65. There was statistically significant difference between DM+VEGF group and all other groups. (p<0,05). 11These results suggest that, VEGF released from calcium alginate microspheres, in a controlled release system, improves epithelization and wound angiogenesis in mice diabetic wound model. 12