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This study aimed to investigate the effects of iontophoresis and hyaluronic acid (HA) combined with a gold nanoparticle (GNP) solution in an excisional wound model. Fifty Wistar rats (n = 10/group) were randomly assigned to the following groups: excisional wound (EW); EW + MC; EW + MC + HA; EW + MC + GNPs; and EW + MC + HA + GNPs. The animals were induced to a circular excision, and treatment started 24 h after injury with microcurrents (300 µA) containing gel with HA (0.9%) and/or GNPs (30 mg/L) in the electrodes (1 mL) for 7 days. The animals were euthanized 12 h after the last treatment application. The results demonstrate a reduction in the levels of pro-inflammatory cytokines (IFNϒ, IL-1β, TNFα, and IL-6) in the group in which the therapies were combined, and they show increased levels of anti-inflammatory cytokines (IL-4 and IL-10) and growth factors (FGF and TGF-β) in the EW + MC + HA and EW + MC + HA + GNPs groups. As for the levels of dichlorofluorescein (DCF) and nitrite, as well as oxidative damage (carbonyl and sulfhydryl), they decreased in the combined therapy group when compared to the control group. Regarding antioxidant defense, there was an increase in glutathione (GSH) and a decrease in superoxide dismutase (SOD) in the combined therapy group. A histological analysis showed reduced inflammatory infiltrate in the MC-treated groups and in the combination therapy group. There was an increase in the wound contraction rate in all treated groups when compared to the control group, proving that the proposed therapies are effective in the epithelial healing process. The results of this study demonstrate that the therapies in combination favor the tissue repair process more significantly than the therapies in isolation.

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