Local Application of Transcutaneous Carbon Dioxide Paste Decreases Inflammation and Accelerates Wound Healing

Introduction: Delayed wound healing after surgery lowers the long-term quality of a patient’s life and leads to discomfort and pain. However, treatments for wound healing are often difficult and have not yet been fully established. In this study, we investigated the effect of a special paste that can be administered transdermally and holds a non-gaseous carbon dioxide (CO(2)) source in its carrier, which can be applied to the head and neck region for wound healing in a rat skin defect model. Methods: Forty-eight Sprague Dawley rats were randomized into control and CO(2) groups. We punched a 6.2-mm wound on the back of each rat. The control rats were left untreated, whereas rats in the CO(2) group were treated with the CO(2) paste every day after surgery. We evaluated wound healing 3, 7, 14, and 21 days after wounding by analyzing the diameter of the wound, gene expression of inflammatory markers vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β, hypoxia-inducible factor (HIF)-1α, interleukin (IL)-1β, and IL-6 using quantitative real-time polymerase chain reaction, hematoxylin and eosin, and immunohistochemical staining patterns. Results: Rats in the CO(2) group showed accelerated wound healing compared to those in the control group. Furthermore, VEGF and TGF-β were overexpressed, whereas HIF-1α, IL-1β, and IL-6 were downregulated in the rats treated with CO(2). Immunohistochemical analysis also revealed similar patterns of expression. Conclusion: Taken together, the CO(2) paste promoted wound healing by regulating the hypoxic environment, reducing inflammation, and accelerating angiogenesis.