Capacitive–Resistive Electric Transfer (CRET, or Tecar therapy) uses radiofrequency currents (typically 448 kHz) that can trigger cellular regeneration through both thermal and subthermal bioelectrical effects. Previous studies had shown Tecar’s ability to stimulate stem cell proliferation and differentiation, but the molecular mechanisms driving its effects on skin repair were not fully understood.This study explored how subthermal 448 kHz Tecar currents affect human keratinocytes and dermal fibroblasts, the two main cell types responsible for epithelial wound closure and dermal remodeling. The goal was to identify how CRET currents influence cellular proliferation, migration, and the expression of proteins regulating adhesion and motility.
Human dermal fibroblasts and HaCaT keratinocytes were cultured and intermittently exposed to 448 kHz sine-wave currents generated by an INDIBA® Activ HCR 902 device. The cells received 5-minute pulses every 4 hours for 6, 12, or 48 hours at either 50 µA/mm² (low) or 100 µA/mm² (high) current densities—both subthermal levels to avoid heating artifacts. Proliferation was quantified using XTT colorimetric assays, migration was assessed via scratch (wound-closure) tests, and protein expression and localization were examined by western blotting and immunofluorescence for vinculin, p-FAK, β-catenin, E-cadherin, MMP-9, and MAPKs (p-ERK1/2, p-p38, p-JNK).
This study demonstrates that subthermal 448 kHz radiofrequency (CRET) currents regulate both proliferation and migration in human fibroblasts and keratinocytes—key drivers of skin repair. The findings reveal that Tecar therapy coordinates these processes rather than accelerating them indiscriminately, guiding cells through the natural phases of wound healing.
In fibroblasts, early stimulation enhanced migration within 6 hours, accompanied by reduced vinculin and p-FAK expression—indicating detachment from the substrate to enable motility. By 12 hours, both proteins localized to the membrane, marking active migration and wound closure. β-catenin rose transiently at 6 hours to promote proliferation, then decreased as fibroblasts stabilized. Simultaneous activation of ERK1/2 and p38 MAPKs supported these pro-migratory, regenerative effects.
In keratinocytes, Tecar induced early vinculin translocation to the membrane but inhibited migration due to p-FAK nuclear inactivation and MMP-9–driven degradation of E-cadherin and β-catenin. These molecular changes disrupted adherens junctions, producing a temporary pause in epithelial migration while fibroblast-led dermal repair advanced. This delay mirrors physiological healing, where fibroblasts reconstruct the dermal matrix before re-epithelialization resumes.
Overall, subthermal CRET currents evoke a coordinated cellular sequence: fibroblast activation and collagen remodeling occur first, followed by keratinocyte proliferation and closure. This regulated pattern confirms Tecar therapy’s ability to bioelectrically orchestrate tissue regeneration, reinforcing its role as a precise, non-thermal modulator of wound repair rather than a simple heating modality.
Subthermal exposure to 448 kHz CRET radiofrequency promotes proliferation and migration in human fibroblasts and keratinocytes via modulation of adhesion proteins (vinculin, β-catenin, E-cadherin) and MAPK signaling pathways (ERK, p38).
This dual regulation—stimulating fibroblast-driven granulation while transiently moderating keratinocyte migration—may explain Tecar therapy’s clinically observed ability to accelerate wound healing and prevent chronic or hypertrophic scarring.
These findings provide strong mechanistic evidence that Tecar therapy exerts bioelectric control over cellular behavior, supporting its use as a non-invasive regenerative therapy for skin repair and tissue recovery.
