Priming with a combination of proangiogenic growth factors improves wound healing in normoglycemic mice

Growth factors and/or angiogenic factors are supposed to improve wound healing. The aim of our study was to evaluate the effects of subcutaneous pretreatment with combinatory proangiogenic factors on wound closure, mechanical properties, vessel density and morphology. Twenty-eight Balb/c mice were divided equally into two 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 to 14 mice before full thickness skin punch biopsy wounding, whereas 14 control animals received three injections of 0.2 ml saline solution. Wound sizes were assessed daily and the repaired tissues were harvested 7 days after complete wound closure. Complete closure (≥95% healing of initial wound area) was reached in all proangiogenic pretreated animals on day 10, whereas controls needed 13 days for complete closure. Tensile strengths were nearly twofold higher compared to the controls (p≤0.01). The punch biopsy material revealed 4.2-fold higher vessel densities in the proangiogenic pretreated group. On day 17, the vessel densities in the proangiogenic pretreated wounds were also 3.2‑fold higher compared to the untreated controls. No significant differences were seen in the collagen ratio. Pretreatment with proangiogenic factors revealed several significant effects on wound healing: faster time to closure, a higher vessel density and a better functional outcome. These results suggest a beneficial effect of pretreatment with combinatory growth factors in mouse skin wounds without impaired wound healing. This might be exploited in further investigations in diabetic healing as a therapeutic approach for elective surgery.