BACKGROUND: Despite great understanding of underlying mechanisms for flap necrosis and advances in surgical techniques, flap necrosis remains a critical issue. In the present study, the authors investigated the efficacy of electroporation-mediated hepatocyte growth factor (HGF) gene delivery to random dorsal skin flaps (McFarlane) to accelerate wound healing and reduce flap necrosis. METHODS: Fifteen male Wistar rats (290 to 320 g) were divided randomly into three groups. Group a, the control group (n = 5), underwent surgery and received no gene transfer. Group b received electroporation-mediated HGF gene delivery 24 hours after surgery as a treatment. Group c received electroporation-mediated HGF gene delivery 24 hours before surgery as prophylaxis (n = 5). Planimetry, laser Doppler imaging, and immunohistochemistry were used to assess the efficacy of HGF gene therapy among the groups. RESULTS: Electroporation-mediated HGF gene delivery significantly decreased flap necrosis percentage compared with the control group in prophylactic and treatment groups (p = 0.0317 and p = 0.0079, respectively) and significantly increased cutaneous perfusion compared with the control group (p = 0.0317 and p = 0.0159, respectively). Moreover, Spearman rank correlation showed a significant negative correlation between flap necrosis percentage and laser index (p = 0.0213 and r = -0.5964, respectively). Furthermore, significantly higher mean CD31 vessel density was detected in treatment and prophylactic groups (p = 0.0079 and p = 0.0159, respectively). In addition, quantitative image analysis revealed significantly higher HGF protein expression in groups b and c (p = 0.0079 and p = 0.0079, respectively). CONCLUSION: These findings suggested in vivo electroporation-mediated HGF gene delivery enhanced viability and vascularity of the ischemic skin flap.
BACKGROUND: Despite great understanding of underlying mechanisms for flap necrosis and advances in surgical techniques, flap necrosis remains a critical issue. In the present study, the authors investigated the efficacy of electroporation-mediated hepatocyte growth factor (HGF) gene delivery to random dorsal skin flaps (McFarlane) to accelerate wound healing and reduce flap necrosis. METHODS: Fifteen male Wistar rats (290 to 320 g) were divided randomly into three groups. Group a, the control group (n = 5), underwent surgery and received no gene transfer. Group b received electroporation-mediated HGF gene delivery 24 hours after surgery as a treatment. Group c received electroporation-mediated HGF gene delivery 24 hours before surgery as prophylaxis (n = 5). Planimetry, laser Doppler imaging, and immunohistochemistry were used to assess the efficacy of HGF gene therapy among the groups. RESULTS: Electroporation-mediated HGF gene delivery significantly decreased flap necrosis percentage compared with the control group in prophylactic and treatment groups (p = 0.0317 and p = 0.0079, respectively) and significantly increased cutaneous perfusion compared with the control group (p = 0.0317 and p = 0.0159, respectively). Moreover, Spearman rank correlation showed a significant negative correlation between flap necrosis percentage and laser index (p = 0.0213 and r = -0.5964, respectively). Furthermore, significantly higher mean CD31 vessel density was detected in treatment and prophylactic groups (p = 0.0079 and p = 0.0159, respectively). In addition, quantitative image analysis revealed significantly higher HGF protein expression in groups b and c (p = 0.0079 and p = 0.0079, respectively). CONCLUSION: These findings suggested in vivo electroporation-mediated HGF gene delivery enhanced viability and vascularity of the ischemic skin flap.
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Authors: Ioana Lese; David Alexander Graf; Catherine Tsai; Adriano Taddeo; Martin Tobias Matter; Mihai A Constantinescu; Inge Katrin Herrmann; Radu Olariu Journal: PLoS One Date: 2018-11-26 Impact factor: 3.240