063 Electroporation‐Facilitated Gene Therapy for Wound Healing

  Using peptide growth factors to improve upon natural wound healing provides promise, but topical application of growth factors has found limited clinical success. Gene therapy has been limited by low transfection efficiency. We are investigating the use of electroporation (EP) in vivo to enhance transfection efficiency and improve wound healing with DNA expression vectors for growth factors. Methods:  To assess plasmid transfection and wound healing, gWIZ luciferase vector and PCDNA3.1/KGF expression vector were used, respectively. Cutaneous wounds were produced via 8 mm‐punch biopsy in Sprague Dawley rats. Healing was impaired by cecal ligation induced sepsis. We used NIH image analysis software and histologic assessment to assess wound closure. Results:  Plasmid Transfection: EP effectively increased expression of gWIZ luciferase vector 53‐fold compared to vector without EP (p < 0.001). We demonstrated that transfection was localized to skin when transfected skin was reflected to reveal underlying muscle. We found that EP‐assisted transfection lasted for 30 days, which is appropriate for treatment of wound healing. Wound Healing:  Using PCDNA3.1/KGF expression vector and EP wounds were 60% smaller on day 12 versus vector without EP (p < 0.009). We assessed quality of healing with a histologic scoring system grading quality of epithelial coverage, organization of scar and resolution of inflammation. KGF vector + EP score of 3.0 +/− 0.3 was better than that of 1.8 +/− 0.3 for treatment with vector alone (p < 0.05). Conclusions:  These results demonstrate the capacity of electroporation‐facilitated transfection with DNA plasmid expression vector for growth factor to improve wound healing. Acknowledgments:  Funding from USAMRMC PRMRP DAMDI7‐03‐1‐0029 and Maryland State Firefighters Fund