Chimeric VEGF-ENZ7/PlGF Specifically Binding to VEGFR-2 Accelerates Skin Wound Healing via Enhancement of Neovascularization

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Objective—VEGF-ENZ7/PlGF molecules composed of Orf virus-derived VEGF-ENZ7 and human PlGF1 were previously proven to be potent angiogenic factors stimulating angiogenesis without significant enhancement of vascular leakage and inflammation in vivo. For its future clinical application, there is a pressing need to better understand the beneficial effects of VEGF-ENZ7/PlGF during wound healing in adulthood.Methods and Results—In this study, several angiogenic factors were administrated to skin punched wounds of both wild-type and diabetic mice. The treatment with VEGF-ENZ7/PlGF accelerated wound closure accompanied with enhanced angiogenesis, the process was occurring slightly faster than that in VEGF-A164 group. Moreover, the macrophage infiltration and lymphangiogenesis level in healed wounds were strikingly lower in VEGF-ENZ7/PlGF group than VEGF-A164 group, suggesting that the increased inflammation was the key issue preventing speedy wound healing of VEGF-A164–treated skin. Considering clinical safety, we further examined the antigenicity of chimeric VEGF-ENZ7/PlGF. Compared with the original VEGF-ENZ7, the immunogenicity of VEGF-ENZ7/PlGF molecules was markedly decreased in mice and squirrel monkeys with the increase of PlGF1 humanized ratio.Conclusion—These results indicate that VEGF-ENZ7/PlGF molecules are superior to VEGF-A for the acceleration of either normal or delayed skin wound healing and might be regarded as potential drugs in therapeutic angiogenesis.

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