Effects of vascular endothelial growth factor on wound closure rates in the genetically diabetic mouse model

Abstract

Impaired wound healing is characteristic of diabetic patients. Potential reasons include poor inflammatory response, granulation tissue formation, and abnormal patterns of cytokine release and response. Vascular endothelial growth factor, abnormally regulated during healing in diabetics, is the major factor stimulating angiogenesis during normal wound healing. We tested our hypothesis that topically applied vascular endothelial growth factor would improve wound closure rates in diabetic animals in a full-thickness wound model in genetically diabetic mice (C57 BL/KsJ db/db). Animals received either 1.0 micro g of vascular endothelial growth factor165 or polyethylene glycol alone topically to wounds daily between days 0 and 4 post-wounding. Wound area was measured at days 0, 5, 10, 15, and 21. Data were analyzed using probit analysis and expressed as length-of-time (LT) to 50, 90, and 95% wound closure. Among untreated animals, nondiabetics had an LT50 of 8.5 days (fiducial limits 8.3-8.7), while diabetics had an LT50 of 15.8 days (15.6-16.1). Vascular endothelial growth factor-treated animals had LT50 values of 7.8 (7.6-8.1) and 11.8 days (11.6-12.0) for nondiabetics and diabetics, respectively, representing a 25% improvement in time to 50% closure in treated diabetics. We conclude that topically applied vascular endothelial growth factor improves time to wound closure in the genetically diabetic mouse model.

Current status of genetic modulation of growth factors in wound repair (Review)

“…Topically applied VEGF improves granulation tissue formation in ischaemic rabbit wounds, although it has no effect on epithelium formation (44). Topical VEGF has recently been found to improve wound closure by 25% in a diabetic mouse model, perhaps because of reduced VEGF production by macrophages, neutrophils and keratinocytes in diabetic mice (83). Similar findings of decreased VEGF in diabetic wounds have been observed in other cutaneous wound healing models (84) and tissue samples from chronic wounds (85,86).…”

Wound Healing Delay in the ZDSD Rat

“…In contrast, the non-obese diabetic (NOD) and the leptindeficient (ob/ob) lines are examples of commonly used animal models with inherited propensity to development of diabetes mellitus (22)(23)(24). Animal models have been described for healing of excisional (25)(26)(27), incisional (28,29), and burn wounds (30,31), and a major emphasis has been placed on healing in diabetic subjects. Excisional wound models are the most common, largely because wound creation is straightforward and processes such as epithelialization, angiogenesis, and scar formation can be readily assessed (32).…”

Low‐level light stimulates excisional wound healing in mice

“…Here, in addition to the BALB/c mice, responses to LLLT were tested in SKH1 and C57BL/6 mice. SKH1 is a hairless non-pedigreed immunocompetent mouse on an albino background, while C57BL/6 is an inbred pigmented strain widely used for transgenic and knockout models [37]. The differences in healing responses between BALB/c and C57BL/6 mice were described in the model of ear punch [38].…”