Adenovirus-Mediated Expression of Keratinocyte Growth Factor Promotes Secondary Flap Necrotic Wound Healing in an Extended Animal Model

Abstract

No effective treatments have been found for flap necrosis. Animal models that focus on the initial flap viability are inappropriate for necrotic wound studies. Keratinocyte growth factor (KGF) promotes keratinocyte proliferation with stronger activity and fewer complications and thus may be useful for necrotic flap wound healing. Rats with modified flap necrosis were randomly divided into four groups. An adenoviral vector expressing KGF was injected subdermally in the back of the animals after necrosis began. The expression and effect of KGF was assessed by real-time polymerase chain reaction, enzyme-linked immunoassay, and transwell, and wound healing was monitored. The plasmid and adenovirus were able to express KGF and stimulate epithelial cell growth (p = 0.029). Histology showed that the necrosis healed fastest in the KGF administration group than in the control groups (p < 0.01). The adenovirus-mediated KGF (Ad-KGF) group had the thickest epithelium on days 15 (p = 0.044) and 25 (p = 0.014). The KGF level in the blood serum soared 10 and 15 days postoperatively (p < 0.01) but returned to baseline by day 25 (p = 0.561). The KGF mRNA levels in vivo increased dramatically in the Ad-KGF group (p = 0.037). The extended flap model is applicable in necrotic wound study. Keratinocyte growth factor can promote secondary necrotic flap wound healing, and administration of KGF can be achieved by an adenoviral vector.