ABSTRACT Purpose: To evaluate exogenous hyaluronic acid (HA) derived from bacterial fermentation through enteral and parenteral routes in ischemic skin flaps induced in rats, using clinical and histological exams; and interleukins (IL) as tissue inflammatory biomarkers. Methods: Sixty-four male adults Wistar rats with ischemic skin flaps on the dorsum were randomized into four groups, based on the treatment protocol: subcutaneous administration of saline solution (0.9%) (GI); oral administration of distilled water (GII); subcutaneous administration of HA (0.3%) (GIII); and oral administration of HA (1%) (GIV). Flaps of all groups were comparable regarding clinical and macroscopic evaluation, histological examination, pro-inflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor-α) and anti-inflammatory cytokine IL-10. Results: A lower percentage of necrosis was identified in flaps treated with subcutaneous administration of HA (0.3%). The pro- and anti-inflammatory cytokines, epidermis thickness, blood vessels, and inflammatory cells showed statistically significant inter-group and intra-group differences (p < 0.05). Conclusions: High molecular HA (1,400 ~ 2,000 kDa) administrated by subcutaneous or oral route exhibited beneficial effects in ischemic skin flaps of rats. However, subcutaneous administration of HA (0.3%) showed better results in terms of the percentage of necrosis and epithelialization. Purpose (HA exams IL (IL biomarkers Methods Sixtyfour Sixty protocol 0.9% 09 0 9 (0.9% GI (GI) GII (GII) 0.3% 03 3 (0.3% GIII (GIII) 1% 1 (1% GIV. GIV . (GIV) evaluation examination proinflammatory pro IL1β, IL1β ILβ 1β, 1β β (IL-1β IL6, IL6 6, 6 IL-6 factorα factor α factor-α antiinflammatory anti IL10. IL10 10. 10 IL-10 Results 0.3%. thickness vessels intergroup inter group intragroup intra p 0.05. 005 0.05 05 0.05) Conclusions 1,400 1400 400 (1,40 2000 2 000 2,00 kDa However epithelialization 0.9 (0.9 (GI (GII 0.3 (0.3 (GIII (1 (GIV IL- IL1 IL-1 00 0.0 1,40 140 40 (1,4 200 2,0 0. (0. ( 1,4 14 4 (1, 20 2, (0 1,

ABSTRACT Purpose: This study aimed to evaluate the effects of ozone therapy applied topically and/or by bagging on the healing of clean wounds induced in rat’s skin. Methods: One hundred and twenty male rats of about 16 weeks old was divided into five groups: G1) saline solution (0.9%); G2) sunflower oil; G3) ozonated sunflower oil; G4) ozone bagging; G5) association of ozonated sunflower oil and ozone bagging. The wounds were evaluated through macroscopic, morphometric, histopathologic, and tensile strength analyses. Results: Analysis among groups showed a lower percentage of wound contraction in G1 compared to G4 only in M7D. The tensile strength of the wounds showed differences among groups in the seventh (M7D) and the 14th (M14D) postoperative day, and among time points in G1 (M14D > M7D). The elongation of the wounds showed differences in G3 (M7D > M14D). Histological evaluation of the wounds showed significant change in bleeding, mixed to mononuclear infiltrate, congestion, and tissue disorganization for tissue organization between groups and time points. Conclusions: Ozone therapy applied topically and/or by bagging was not deleterious to the healing of clean wounds induced in rat’s skin, but ozone bagging showed the best contribution to the healing process. Purpose andor or rat s skin Methods 1 G 0.9% 09 0 9 (0.9%) G2 G5 macroscopic morphometric histopathologic analyses Results M7D MD M D th M14D day . M7D) M14D. M14D) bleeding infiltrate congestion Conclusions process 0.9 (0.9% 0. (0.9 (0. (0 (