Wound Repair and Extremely Low Frequency-Electromagnetic Field: Insight from In Vitro Study and Potential Clinical Application

Abstract

Wound healing is a complex, staged process. It involves extensive communication between the different cellular constituents of various compartments of the skin and its extracellular matrix (ECM). Different signaling pathways are determined by a mutual influence on each other, resulting in a dynamic and complex crosstalk. It consists of various dynamic processes including a series of overlapping phases: hemostasis, inflammation response, new tissue formation, and tissue remodeling. Interruption or deregulation of one or more of these phases may lead to non-healing (chronic) wounds. The most important factor among local and systemic exogenous factors leading to a chronic wound is infection with a biofilm presence. In the last few years, an increasing number of reports have evaluated the effects of extremely low frequency (ELF) electromagnetic fields (EMFs) on tissue repair. Each experimental result comes from a single element of this complex process. An interaction between ELF-EMFs and healing has shown to effectively modulate inflammation, protease matrix rearrangement, neo-angiogenesis, senescence, stem-cell proliferation, and epithelialization. These effects are strictly related to the time of exposure, waveform, frequency, and amplitude. In this review, we focus on the effect of ELF-EMFs on different wound healing phases.

Evaluation of Cell Migration and Cytokines Expression Changes under the Radiofrequency Electromagnetic Field on Wound Healing In Vitro Model

“…To promote the WH, several EMFs with different frequencies, square waveform, and intensity have been explored [8,[23][24][25][26][27][28]. In fact, several studies have evaluated the effects of PEMF on chronic diabetic foot ulcers but using different PEMF parameters and with contradictory findings [29,30], suggesting that combinations of intensity and treatment period may produce different effects on extracellular matrix synthesis and remodeling, cell proliferation and migration.…”

“…It has been suggested that reduced or delayed WH may be a consequence of an altered equilibrium between free radicals and antioxidants allowing the wound to proceed unchecked. In fact, in the elderly subject, WH was delayed, and interestingly, the levels of wound antioxidants decrease with aging [23].…”

Differential biological responses of adherent and non-adherent (cancer and non-cancerous) cells to variable extremely low frequency magnetic fields

“…While Helmholtz coils produce fields with limited intensities (less than a few milli Teslas) and the other instruments based on magnets have a very limited range of frequencies, our new design can apply various exposure conditions with a broad range of low frequencies (0–70 Hz/0.001 Hz accuracy) and also the maximum intensity of 150 mT. This range of amplitude and frequency can generate interesting non-ionizing, non-thermal effects 29 which has recently attracted researchers’ attention for their new biomedical applications 10 , 30 , 31 . Moreover, as noted above, the ability of long-time exposures in an optimal culture condition is a prominent feature of our new design.…”

“…At the same time, many studies have reported the positive effects and therapeutic uses of ELF-EMF e.g. in wound repair 8 , 9 , bone repair, pain management 10 , and Alzheimer’s disease (AD) 11 . Recent in vitro and in vivo studies have shown that exposure to ELF-EMF directly influenced human cells where it induced various effects; for instance, altered reactive oxygen species (ROS) levels 12 , increased intracellular Ca 2+ 13 , 14 , changed expression of genes involved in cell cycle, metabolism, autophagy, apoptosis pathways 15 – 17 , and inhibited proliferation 18 , 19 .…”

Wound-Healing Promotion and Anti-Inflammatory Properties of Carvacrol Prodrugs/Hyaluronic Acid Formulations

“…Impaired WH is a result of the failure of normal progression through the phases [ 26 ]. In the last few years, an increasing number of reports have evaluated the effects of pharmacologic or physical modulation of tissue repair [ 27 , 28 , 29 , 30 , 31 ].…”