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

Adv Skin Wound Care. 2025 Dec 29. doi: 10.1097/ASW.0000000000000388. Online ahead of print.

ABSTRACT

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.

PMID:41460215 | DOI:10.1097/ASW.0000000000000388