Trends in wound repair: cellular and molecular basis of regenerative therapy using electromagnetic fields.

Chronic ulceration of the leg represents a major, underestimated problem of modern health care, involving physical and cosmetic impairment and social stigma along with high community costs for patients' treatment. The increasing prevalence of chronic ulcers, currently reported to be as much as 0.3% in the general population, should stimulate identification of more efficacious therapeutic approaches to achieve complete healing. The strategies of regenerative medicine based on small molecules, biomimetic scaffolds, gene or cell therapy, and electromagnetic field manipulation represent some of the modern therapeutic alternatives for wound healing. Here we review in an integrated, interdisciplinary approach the modern cellular and molecular mechanistic concepts regarding the involvement of extremely low frequency electromagnetic fields (ELF-EMF) in the complex process of tissue repair, with particular focus on chronic wounds. The data analysis supports three main effects of electromagnetic fields on the wound healing pathways: 1) an antiinflammatory effect, by modulation of cytokine profile that induces the transition of the healing process from a chronic pro-inflammatory to an anti-inflammatory state; 2) a neo-angiogenic effect, by increased endothelial cells proliferation and tubulization and production of fibroblast growth factor (FGF)-2; and 3) a reepithelialization effect, by stimulation of collagen formation. We believe that utilization of ELF-EMF in larger clinical trials designed to optimize these functional parameters would facilitate a better understanding of ELFEMF- induced healing mechanisms and lead to improved therapeutic outcomes for this disabling condition which is often totally resistant to treatment.