Evaluation of the restorative effect of ozone and chitosan–hyaluronic acid with and without mesenchymal stem cells on wound healing in rats

This study evaluated the effect of ozone, chitosan–hyaluronic (Cs–HA) acid and mesenchymal stem cells (MSCs) on wound healing in rats. A total of 64 rats were randomly divided into four groups: control, ozone, Cs–HA + ozone and Cs–HA + ozone + MSCs. A 5 mm full‐thickness wound was created on the back of each rat. The wound area was measured macroscopically on days 3, 5, 9 and 14. Tissue sections were prepared for histopathological evaluation of inflammation, collagen arrangement, neovascularization and epithelial tissue rearrangement. Macroscopic assessment showed differences in wound area on days 5, 9 and 14. Histopathological examination showed that the Cs–HA + ozone + MSCs and Cs–HA + ozone groups had significantly higher vascularization on day 3 compared to the ozone‐treated and control groups. All treatment groups had significantly better collagen arrangement than the control group. On day 5, no significant difference was observed between different groups. On day 9, the inflammation level in the Cs–HA + ozone + MSCs group was significantly lower than in the other groups. All treatment groups had significantly better vascularization compared to the control group. On day 14, the rate of inflammation was significantly lower in the treatment groups than in the control group. Significantly higher collagen arrangement levels were observed in the Cs–HA + ozone and Cs–HA + ozone + MSCs groups compared to the control and ozone groups. All treatment groups had significantly better epithelial tissue rearrangement than the control group. Overall, the results of this study indicated that treatment with ozone, Cs–HA acid, Cs–HA and MSCs accelerated wound healing in rats. The effect of using Cs–HA acid with mesenchymal cells was better than the other types of treatment. Larger clinical trials are needed to assess these factors for improving chronic wound treatment.