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Wound healing presents a unique challenge for patients with diabetes. Gas therapies have gained significant attention in the wound-healing community. Carbon monoxide (CO) is a small molecule that is well known for its immune-modulating properties when administered at sublethal concentrations. CO is currently in clinical trials for lung disease, sickle cell anemia, and organ transplantation. Here, we investigated the effects of CO in an in vitro wound-healing model and subsequently developed and tested CO gas-entrapping materials (CO-GEMs) for topical application on wounds to promote healing. In this study, we report the efficacy of CO-GEMs in treating full-thickness wounds and pressure ulcers in diabetic mouse models. Collectively, our findings demonstrate that these novel gas entrapping materials could serve as an alternative therapy to both protect the wound bed and promote healing and replace bulky hyperbaric chambers, standard gauze wound dressings, or expensive skin grafts. 

Abstract Modulation of autophagy, specifically its inhibition, stands to transform the capacity to effectively treat a broad range of cancers. However, the clinical efficacy of autophagy inhibitors has been inconsistent. To delineate clinical and epidemiological features associated with autophagy inhibition and a positive oncological clinical response, a retrospective analysis of patients is conducted treated with hydroxychloroquine, a known autophagy inhibitor. A direct correlation between smoking status and inhibition of autophagy with hydroxychloroquine is identified. Recognizing that smoking is associated with elevated circulating levels of carbon monoxide (CO), it is hypothesized that supplemental CO can amplify autophagy inhibition. A novel, gas‐entrapping material containing CO in a pre‐clinical model is applied and demonstrated that CO can dramatically increase the cytotoxicity of autophagy inhibitors and significantly inhibit the growth of tumors when used in combination. These data support the notion that safe, therapeutic levels of CO can markedly enhance the efficacy of autophagy inhibitors, opening a promising new frontier in the quest to improve cancer therapies.