Limited Treatment Options for Diabetic Wounds: Barriers to Clinical Translation Despite Therapeutic Success in Murine Models.

Significance: Millions of people worldwide suffer from diabetes mellitus and its complications, including chronic diabetic wounds. To date, there are few widely successful clinical therapies specific to diabetic wounds beyond general wound care, despite the vast number of scientific discoveries in the pathogenesis of defective healing in diabetes. Recent Advances: In recent years, murine animal models of diabetes have enabled the investigation of many possible therapeutics for diabetic wound care. These include specific cell types, growth factors, cytokines, peptides, small molecules, plant extracts, microRNAs, extracellular vesicles, novel wound dressings, mechanical interventions, bioengineered materials, and more. Critical Issues: Despite many research discoveries, few have been translated from their success in murine models to clinical use in humans. This massive gap between bench discovery and bedside application begs the simple and critical question: what is still missing? The complexity and multiplicity of the diabetic wound makes it an immensely challenging therapeutic target, and this lopsided progress highlights the need for new methods to overcome the bench-to-bedside barrier. How can laboratory discoveries in animal models be effectively translated to novel clinical therapies for human patients? Future Directions: As research continues to decipher deficient healing in diabetes, new approaches and considerations are required to ensure that these discoveries can become translational, clinically usable therapies. Clinical progress requires the development of new, more accurate models of the human disease state, multifaceted investigations that address multiple critical components in wound repair, and more innovative research strategies that harness both the existing knowledge and the potential of new advances across disciplines.