Effects of Extremely Low-Frequency Sinusoidal Electromagnetic Field Therapy on Survival and Vascularization in a Rat Random-Pattern Skin Flap Model

Abstract Aim This study aimed to evaluate the dose-dependent effects of extremely low-frequency sinusoidal electromagnetic fields (ELF-EMF) on survival and vascularization of random-pattern dorsal skin flaps in rats and to investigate associated histological and molecular changes. Materials and Methods Twenty-one male Sprague-Dawley rats underwent McFarlane dorsal random-pattern flap surgery and were randomly assigned to three groups (n = 7/group): control, low-dose ELF-EMF (0.2 mT), and high-dose ELF-EMF (5 mT). Sinusoidal ELF-EMF exposure (50 Hz) was administered twice daily for 15 minutes for 14 postoperative days. Flap viability was assessed by digital planimetry. Histological evaluation included hematoxylin-eosin and Masson's trichrome staining. TNF-α immunohistochemistry and quantitative real-time PCR analysis of apoptosis-, inflammation-, and angiogenesis-related genes were performed. Results The low-dose ELF-EMF group demonstrated significantly higher flap viability than both the control and high-dose groups (76.3 ± 6.9% vs. 55.2 ± 9.1% and 55.7 ± 11.3%, respectively; p < 0.05). Histological analyses showed enhanced re-epithelialization, increased vascularization, improved collagen organization, and reduced inflammatory cell infiltration in the low-dose group. High-dose ELF-EMF did not improve flap survival and was associated with suppression of VEGF and MAPK pathway-related gene expression. The discordance between increased TNF-α mRNA expression and reduced immunohistochemical staining in the low-dose group suggests temporally dynamic and post-transcriptional regulation. Conclusion Low-dose sinusoidal ELF-EMF improved survival and histological markers of repair in a rat random-pattern skin flap model, whereas high-dose exposure did not confer benefit. These findings support the existence of a dose-dependent biological window for ELF-EMF therapy. Given the exploratory preclinical nature of the study, further mechanistic and translational investigations are required before clinical application.