Novel therapeutic targets for diabetes-related wounds or ulcers: an update on preclinical and clinical research.

Diabetes-related wounds, particularly diabetes-related foot ulcers, are mainly caused by lack of foot sensation and high plantar tissue stress secondary to peripheral neuropathy, ischemia secondary to peripheral artery disease, and dysfunctional wound healing. Current management of diabetes-related wounds involves the offloading of high foot pressures and the treatment of ischemia through revascularization. Despite these treatments, the global burden of diabetes-related wounds is growing, and thus, novel therapies are needed. The normal wound healing process is a coordinated remodeling process orchestrated by fibroblasts, endothelial cells, phagocytes, and platelets, controlled by an array of growth factors. In diabetes-related wounds, these coordinated processes are dysfunctional. The past animal model and human research suggest that prolonged wound inflammation, failure to adequately correct ischemia, and impaired wound maturation are key therapeutic targets to improve diabetes-related wound healing. This review summarizes recent preclinical and clinical research on novel diabetes-related wound treatments. Animal models of diabetes-related wounds and recent studies testing novel therapeutic agents in these models are described. Findings from clinical trials are also discussed. Finally, challenges to identifying and implementing novel therapies are described. Given the growing volume of promising drug therapies currently under investigation, it is expected within the next decade, that diabetes-related wound treatment will be transformed.