Priming with a combination of proangiogenic growth factors enhances wound healing in streptozotocin-induced diabetes in mice

Eur Surg Res. 2011;47(2):81-9. doi: 10.1159/000328143. Epub 2011 Jun 30.

Abstract

Background: Numerous proangiogenic growth factors have been shown to improve impaired wound healing. This study evaluated the effects of subcutaneous pretreatment with a combination of proangiogenic growth factors on wound closure, mechanical properties, vessel density, and morphology.

Methods: Thirty-six Balb/c mice with streptozotocin-induced diabetes were divided into 3 groups. A mixture of VEGF (35.0 μg), bFGF (2.5 μg), and PDGF (3.5 μg) was administered subcutaneously 3, 5, and 7 days prior to wounding in the first group, whereas the second group received three doses of 3.5 μg PDGF. Wound sizes were assessed daily and the repaired tissues were harvested 7 days after wound closure.

Results: Complete closure (≥95% healing of initial wound area) was reached in all proangiogenic pretreated animals by day 17, whereas the PDGF monotherapy group needed up to 20 days for complete closure. By the time of tissue harvesting on day 24, complete closure was not reached in all control animals. Punch biopsy material revealed 1.6-fold higher vessel densities in the proangiogenic combination-pretreated group than in the controls.

Conclusions: Proangiogenic priming revealed several significant effects on diabetic wound healing: faster time to closure, a higher vessel density, and improved functional outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenic Proteins / administration & dosage*
  • Animals
  • Collagen / metabolism
  • Diabetes Complications / drug therapy
  • Diabetes Complications / pathology
  • Diabetes Complications / physiopathology
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / pathology*
  • Diabetes Mellitus, Experimental / physiopathology
  • Female
  • Fibroblast Growth Factor 2 / administration & dosage
  • Mice
  • Mice, Inbred BALB C
  • Neovascularization, Physiologic / drug effects
  • Platelet-Derived Growth Factor / administration & dosage
  • Skin / blood supply
  • Skin / drug effects
  • Skin / injuries
  • Skin / pathology
  • Skin / physiopathology
  • Skin Temperature / drug effects
  • Tensile Strength / drug effects
  • Vascular Endothelial Growth Factor A / administration & dosage
  • Wound Healing / drug effects*

Substances

  • Angiogenic Proteins
  • Platelet-Derived Growth Factor
  • Vascular Endothelial Growth Factor A
  • platelet-derived growth factor A
  • vascular endothelial growth factor A, mouse
  • Fibroblast Growth Factor 2
  • Collagen