Transcutaneous Applications of Carbon Dioxide in Wound Healing

The local administration of carbon dioxide through the skin, often termed carboxytherapy or transcutaneous CO2 therapy, has emerged as a non-invasive modality to accelerate wound repair. By increasing subcutaneous CO2 tension, this approach exploits the Bohr effect to enhance oxygen release from haemoglobin, promote vasodilation and hyperaemia and stimulate angiogenesis independently of traditional hypoxia-driven pathways. At the cellular level, elevated CO2 modulates inflammatory cascades, downregulates pro-inflammatory cytokines and activates growth factors such as vascular endothelial growth factor and transforming growth factor β. Various delivery platforms—including gaseous insufflation, hydrogels, topical pastes and foot baths—have been adapted to target chronic venous ulcers, diabetic foot lesions, osteomyelitic defects and surgical wounds. Such techniques not only support granulation tissue formation and collagen deposition but also offer a cost-effective, patient-friendly alternative or adjunct to standard debridement and dressings. Ongoing research continues to refine protocols for concentration, application duration and frequency, while elucidating the molecular mediators that underpin CO2-induced tissue homeostasis and regeneration.

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Transcutaneous Applications of Carbon Dioxide in Wound Healing publication trend

The graph below shows the total number of articles in transcutaneous applications of carbon dioxide in wound healing across all publications each year (not limited to Nature Index journals).

Technical terms

Transcutaneous application: delivery of a compound across the skin surface into underlying tissues.

Angiogenesis: process through which new capillaries form from pre-existing blood vessels.

Bohr effect: shift in haemoglobin–oxygen dissociation curve caused by elevated carbon dioxide and decreased pH, facilitating oxygen release in tissues.

Hypoxia-inducible factor 1α: transcriptional regulator activated under low oxygen conditions that promotes expression of genes involved in vascular growth and metabolism.

References

1. The Tissue Response to Hypoxia: How Therapeutic Carbon Dioxide Moves the Response toward Homeostasis and Away from Instability. International Journal of Molecular Sciences (2023).
2. Osteolytic metatarsal osteomyelitis regenerated by combined treatment of artificial carbon dioxide foot bathing and povidone–iodine sugar ointment: a case report. Journal of Medical Case Reports (2022).
3. Local Application of Transcutaneous Carbon Dioxide Paste Decreases Inflammation and Accelerates Wound Healing. Cureus (2021).