Topical gaseous NO and CO therapy in acceleration of wound healing

The GEMI Fund awards grants for the development of new and innovative research that addresses clinical use of gases relating to the treatment, prevention or diagnosis of diseases. The grants amount to a total of 1 million dollars every other year, which makes the GEMI Fund a significant contributor to this area.
The first round of GEMI Fund grants were announced and celebrated at a ceremony in October 2003 in Boston, USA. One million dollars were shared by seven scientists from the USA, Germany and Portugal and Dr Malinski was one them.

Professor Tadeusz Malinski of the Biochemistry laboratory of Ohio University in Athens, Ohio, USA was awarded his grant in 2003 for research on ‘topical gaseous nitric oxide and carbon monoxide therapy in acceleration of wound healing’.

The studies were performed using mice and rats and three types of wounds: skin incision wounds, excision wounds (biopsy punch) and deep surgical wounds. This latter type was also studied because of the high importance of the acceleration of healing of these wounds and because of their impact on time and cost of hospitalization. The distribution of nitric oxide (NO), superoxide (02-), carbon monoxide (CO) and peroxynitrite (ONOO-) and their concentrations was studied for a period of 12-25 days. A nanomedical approach was used with nanosensors for both in vivo and in vitro measurements of NO, 02-, CO and ONOO-. The studies considered different types of gas membrane and gas delivery systems as well as different gas concentrations and exposure times.

Healing was evaluated based on the level of collagen, on morphometric analysis (quantification of tissue and subcellular components) using light and electron scan microscopy, and on blood flow and breaking strength.

The studies demonstrated that the healing process of wounds is dependent on the level of a protective nitric oxide and of cytotoxic ONOO (peroxynitrite) which can be produced in a wound. The balance between these two molecules is also highly significant. Topical treatment with gaseous NO, CO (and mixtures of the two) was found to affect this balance favourably and to accelerate wound healing by up to 40% in rats and mice. Further studies may show if these data can be confirmed and translated into human use.