Abstract
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 (CO2) 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 CO2 groups. We punched a 6.2-mm wound on the back of each rat. The control rats were left untreated, whereas rats in the CO2 group were treated with the CO2 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 CO2 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 CO2. Immunohistochemical analysis also revealed similar patterns of expression.Conclusion: Taken together, the CO2 paste promoted wound healing by regulating the hypoxic environment, reducing inflammation, and accelerating angiogenesis.
Highlights
Delayed wound healing after surgery lowers the long-term quality of a patient’s life and leads to discomfort and pain
vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β were overexpressed, whereas hypoxia-inducible factor (HIF)-1α, IL-1β, and IL-6 were downregulated in the rats treated with CO2
We have previously reported the use of a topical cutaneous CO2/hydrogel to accelerate the repair of a fracture and enhance angiogenesis and blood flow [8]
Summary
Delayed wound healing after surgery lowers the long-term quality of a patient’s life and leads to discomfort and pain. Delayed wound healing after surgery or injury causes discomfort and pain, thereby lowering the long-term quality of life in patients. After head and neck surgery and injury, a delay in wound healing is likely to cause infection, prolonged and expensive hospital stay, and further delay in additional treatment [3]. Transcutaneous carbon dioxide (CO2) therapy has been developed for use in humans and animal models to evaluate its efficacy in treating various conditions, for example, medical and beauty treatments [5,6,7]. This therapeutic strategy is safe and benefits human health by affecting various biological processes. Transcutaneous CO2 therapy improves the blood flow and angiogenesis in skin flaps [9] and stimulates muscle injury repair [10]
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