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 (C) 2012 John Wiley & Sons, Ltd.