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Percutaneous collagen induction (PCI) is an alternative treatment for skin dysfunctions, it aims to stimulate collagen production by encouraging normal wound healing that occurs after any trauma by inducing microlesions; also it may be potentiated with the association with drugs such as hyaluronic acid (HA). Our objective was to evaluate the effects of PCI associated with hyaluronic acid (0.9%) on inflammatory process, oxidative stress, and collagen production in rat epidermis. For the study, 36 adult Wistar rats were randomly divided into 6 groups (n = 6): Control; PCI 0.5; PCI 1.0; HA; PCI 0.5 + HA; and PCI 1.0 + HA. The animals were anesthetized, trichotomized, and the application of therapies was performed once; After 7 days, the animals were euthanized for removal of the skin region. Levels of pro-inflammatory (IL1, IL6, TNFα), anti-inflammatory (IL4 and IL10) cytokines and growth factors (FGF, TGFβ) were evaluated, besides oxidative stress parameters and histological analysis. In combination groups, there is a decrease in TNFα compared with the control and PCI groups in contrast to a significant increase in anti-inflammatory cytokines and growth factors. Oxidant and oxidative damage levels showed a significant decrease in PCI + HA groups in relation to PCI groups while antioxidant defense increased in PCI + HA groups compared with the control group. The number of fibroblasts was increased in the PCI 1.0 group in relation to the control, HA, and PCI 0.5. The number of blood vessels and collagen area was increased in groups PCI and PCI + HA compared with the HA group. We conclude that the combination of PCI with HA is able to accelerate the acute inflammatory process, reducing its deleterious effects and anticipating the chronic response, contributing to tissue repair.

Healing is the process responsible for restoring the integrity of the body's internal or external structures when they rupture. Photobiomodulation (PBM) stands out as one of the most efficient resources in the treatment of epithelial lesions, as well as hyaluronic acid (HA), which has been emerging as a new molecule for the treatment of dermal and epidermal lesions. The biological application of gold nanoparticles (GNPs) shows promising results. This study aimed to investigate the possible anti-inflammatory and antioxidant effects of the association between PBM and GNPs-linked HA in an epithelial lesion model. Fifty Wistar rats were randomly distributed in the Control Group (CG); (PBM); (PBM + HA); (PBM + GNPs); (PBM + GNPs-HA). The animals were anesthetized, trichotomized, and induced to a surgical incision in the dorsal region. Topical treatment with HA (0.9%) and/or GNPs (30 mg/kg) occurred daily associated with 904 nm laser irradiation, dose of 5 J/cm 2 , which started 24 h after the lesion and was performed daily until the seventh day. The levels of proinflammatory (IL1 and TNFα), anti-inflammatory (IL10 and IL4) and growth factors (FGF and TGFβ) cytokines and oxidative stress parameters were evaluated, besides histological analysis through inflammatory infiltrate, fibroblasts, new vessels, and collagen production area. Finally, for the analysis of wound size reduction, digital images were performed and subsequently analyzed by the IMAGEJ software. The treated groups showed a decrease in proinflammatory cytokine levels and an increase in anti-inflammatory cytokines. TGFβ and FGF levels also increased in the treated groups, especially in the combination therapy group (PBM + GNPs-HA). Regarding the oxidative stress parameters, MPO, DCF, and Nitrite levels decreased in the treated groups, as well as the oxidative damage (Carbonyl and Thiol groups). In contrast, antioxidant defense increased in the groups with the appropriate therapies proposed compared to the control group. Histological sections were analyzed where the inflammatory infiltrate was lower in the PBM + GNPs-HA group. The number of fibroblasts was higher in the PBM and PBM + HA treated groups, whereas collagen production was higher in all treated groups. Finally, in the analysis of the wound area contraction, the injury group presented a larger area in cm 2 compared to the other groups. Taken together, these results allow us to observe that the combination of PBM + GNPs-HA optimized the secretion of anti-inflammatory cytokines, proliferation and cell differentiation growth factors, and made an earlier transition to the chronic phase, contributing to the repair process.