Carbon monoxide-infused foam promotes healing in diabetic skin wounds

Drawing on modern culinary techniques, researchers have developed a carbon-monoxide-infused foam that can be applied topically to wounds and improves healing in models of diabetic wounds and pressure ulcers. The results of the study, led by James Byrne, MD, PhD, University of Iowa assistant professor of radiation oncology and biomedical engineering, were published March 12 in Device, a Cell Press journal.   

“Certain gases, like carbon monoxide, are known to have therapeutic properties if they are delivered in the right concentration at the right place. Our novel gas-entrapping materials, which can be formulated as foams or gels or even solids, allow us to deliver gases in a safe, prolonged fashion directly to the site where the therapy is needed,” Byrne explains. 

Ultimately, Byrne and his colleagues at Harvard Medical School and Massachusetts Institute of Technology (MIT) hope to start a new company around the technology. In addition to wound-healing, the researchers are also exploring the use of gas-entrapping materials (GEMs) in various cancer therapies. 

Novel gas-entrapping materials could one day provide human therapies for diabetes 

Diabetes affects almost 39 million Americans and causes numerous health complications. One major consequence of diabetes is impaired wound healing, which results from chronic inflammation, a key feature of diabetes, and high blood sugar levels, which can fuel bacterial infections. Skin wounds and ulcers that do not heal well can be particularly problematic for people with diabetes, sometimes leading to serious infections, amputation, or even death. 

Recent studies have shown that topical gas therapies may have potential for improving wound healing. Carbon monoxide (CO), for example, is generally thought of as a toxic gas, but localized in the right concentration, it can also deliver unique immune modulating effects that may be beneficial. 

In the new study, Byrne and his colleagues first showed that exposure to carbon monoxide enhances migration of human skin cells in a petri dish, a characteristic that could help the wound-healing process. They then developed a novel foam made from hyaluronic acid—a substance used in many skincare products—infused with carbon monoxide. The foam can be applied safely to wounds and allows for prolonged delivery of the gas directly at the wound site for therapy. The GEM also contained silver nanoparticles, which have antimicrobial properties and have been shown to promote wound healing. 

Using mouse models of diabetic wounds, the researchers showed that the CO-foam promoted healing responses in deep skin wounds and pressure ulcers when compared to a foam infused with nitrogen, which does not have the same immune boosting properties as carbon monoxide, or untreated wounds. 

“Topical application of the CO-foam maximized the local delivery of carbon monoxide while maintaining safe levels of systemic carbon monoxide, and the two types of diabetic wounds healed better and faster than untreated wounds or wounds treated with inert nitrogen-foam,” Byrne says. “We still need to test this approach in models that more closely resemble human diabetic wounds, but eventually we hope to develop these gas-entrapping materials into human therapies.” 

In addition to Byrne, the research team also included co-first authors Emily Witt and Alexander Leach at the UI, Giovanni Traverso at MIT and Harvard Medical School, and Leo Otterbein at Beth Israel Deaconess Medical Center, Harvard Medical School. UI researchers in the Carver College of Medicine Departments of Radiation Oncology, Otolaryngology, and Pathology, Holden Comprehensive Cancer Center, and the UI Department of Biomedical Engineering, and researchers at Harvard Medical School, MIT, University of North Carolina Wilmington, and University of Toronto, were also part of the team. 

Byrne, Otterbein, and Traverso are co-inventors on a patent application that covers therapeutic carbon monoxide formulations. 

The research was funded in part by grants from the UI Department of Radiation Oncology and Holden Comprehensive Cancer Center at the UI, and from the National Cancer Institute (P30CA086862, K08CA276908), the American Cancer Society, Hope Funds for Cancer Research, the Prostate Cancer Foundation, the U.S. Department of Defense Prostate Cancer Program.