Effect of Electrical Stimulation on Cytokines and Growth Factors Active in the Process of Wound Healing: A Systematic Review of In Vivo Animal Studies and Randomized Clinical Trials.

OBJECTIVE

To systematically review in vivo animal studies and randomized clinical trials (RCTs) analyzing the effects of electrical currents on cytokine and growth factor levels involved in wound healing.

DATA SOURCES: PubMed, EBSCO, Ovid, Elsevier, and online gray literature databases were searched for relevant studies.

STUDY SELECTION: Eligible studies were full-text, English-language in vivo reports or RCTs comparing at least 10 electrically stimulated (ES) wounds with 10 control wounds left untreated or treated with sham ES or nonphysical interventions.

DATA EXTRACTION: Extracted data included ES-induced changes in cytokine and growth factor levels in wounds or blood. Methodologic quality was assessed using the SYRCLE risk-of-bias tool (animal studies) and the PEDro scale (RCTs).

DATA SYNTHESIS: Eight studies (6 in vivo with 349 animals and 2 RCTs with 44 patients with diabetic foot ulcers) published between 2011 and 2021 were analyzed. ES protocols included direct current, low-voltage and high-voltage monophasic, biphasic, and alternating currents applied at sub-sensory to motor intensities. Most in vivo studies reported reduced cytokine levels (IL-1β, IL-6, TNF-α, and IL-10) and increased growth factors (VEGF, FGF-2, EGF, and TGF-β1). RCTs found ES increased VEGF in wounds and blood but did not affect soluble VEGF receptor-2 levels.

CONCLUSIONS

Electrical stimulation favorably modulates cytokine and growth factor expression, supporting faster wound healing. However, due to the limited number and heterogeneity of studies, further high-quality research is required to establish optimal ES parameters.