Effective healing of diabetic skin wounds by using nonviral gene therapy based on minicircle vascular endothelial growth factor DNA and a cationic dendrimer

Background The development of an efficient method to improve the wound healing process is urgently required for diabetic patients suffering a threat of limb amputations. Various growth factors have been proposed for treatment; however, more research still has to be carried out to maintain their curative effect. In the present study, we describe a simple nonviral gene therapy method for improving wound healing. Methods Minicircle plasmid DNA encoding vascular endothelial growth factor (VEGF) was combined with an arginine‐grafted cationic dendrimer, PAM‐RG4. The formed complexes were injected subcutaneously into the skin wounds of diabetic mice. Results Actively proliferating cells in wound tissue were efficiently transfected, resulting in a high level of VEGF expression. Within 6 days after injection, skin wounds in the diabetic mice were generally healed and displayed a well‐ordered dermal structure, which was confirmed by histological staining. Conclusions This simple and effective gene therapy method may represent a powerful tool for the treatment of diabetic foot ulcers and other diseases that are refractory to treatment. Copyright © 2012 John Wiley & Sons, Ltd.