1. ^*Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
2. ^†Department of Bioengineering, School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
3. ^‡Center of Research Pierre Fabre Dermo-Cosmetique, Allee Camille Soula, Cedex, France

Correspondence: Leaf Huang, Center for Pharmacogenetics, University of Pittsburgh, 633 Salk Hall, Pittsburgh, Pennsylvania, USA. Email: Huangl@upmc.edu

Received 9 December 2003; Revised 10 March 2004; Accepted 24 March 2004; Published online 10 September 2004.

Abstract

Electrical stimulation (ES) is a therapeutic treatment for wound healing. Electroporation, a type of ES, is a well-established method for gene delivery. We hypothesize that proper conditions can be found with which both electrical and gene therapies can be additively applied to treat diabetic wound healing. For the studies of transforming growth factor-1 (TGF-1) local expression and therapeutic effects, full thickness excisional wound model of db/db mice was used, we measured TGF-1 cytokine level at 24 h postwounding and examined wounds histologically. Furthermore, wound closure was evaluated by wound-area measurements at each day for 14 d. We found that syringe electrodes are more effective than the conventional caliper electrodes. Furthermore, diabetic skin was more sensitive to the electroporative damage than the normal skin. The optimal condition for diabetic skin was six pulses of 100 V per cm for 20 ms. Under such condition, the healing rate of electrically treated wound was significantly accelerated. Furthermore, when TGF-1 gene was delivered by electric pulses, the healing rate was further enhanced. Five to seven days postapplication of intradermal injection of plasmid TGF-1 followed by electroporation, the wound bed showed an increased reepithelialization rate, collagen synthesis, and angiogenesis. The data indicates that indeed the electric effect and gene effect work synergistic in the genetically diabetic model.