**1. Introduction**

Diabetes mellitus is a worldwide pandemic, affecting 29 million Americans and over 171 million peoples worldwide, resulting in substantial morbidity and mortality, and accounting for an annual healthcare expenditure exceeding \$176 billion in the US alone (Data from the 2014 National diabetes fact sheet; available at http://www.cdc.gov/diabetes/pdfs/data/2014‐report‐

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

estimates-of-diabetes-and-its-burden-in-the-united-states.pdf). This burden of disease is the result of a progressive disease process associated with numerous complications, such as retinopathy, neuropathy, and nephropathy, as well as the development of chronic wounds. Chronic wounds remain the leading cause of hospital admissions and nontraumatic lower extremity amputations in patients with diabetes, with nearly 80% of all amputations performed in patients with diabetes preceded by a diabetic wound [1]. Risk factors for the development of diabetic wounds include the presence of the "pathogenic triad" of neuropathy, ischemia, and trauma [2–4]. In addition, foot deformities, lower extremity edema, and use of inappropriate footwear also contribute to the development of diabetic wounds [2–4].

Despite clinical strategies aimed at prevention and early detection of diabetic neuropathy and diabetic wounds, patients with diabetes continue to have a 12–25% lifetime risk of developing a chronic diabetic wound due to poor patient compliance and progression of the diabetic phenotype [5, 6]. Projections indicate that by 2025 diabetes will affect over 300 million people worldwide, with a rising proportion of the burden borne by patients in developing countries [7, 8]. Given this anticipated rise in the burden of disease attributable to diabetes, and the potential concomitant rise in development of chronic wounds, the impetus for developing more effective wound care strategies cannot be understated.

After injury, patients with diabetes suffer from an impaired wound healing response; the standard wound healing response, in which the tissue passes through consecutive, but overlapping phases of coagulation, inflammation, proliferation, and remodeling, is disrupted [2]. Notably, patients with diabetes demonstrate a phenotype characterized by decreased angiogenesis, impaired leukocyte migration, decreased growth factor production, sustained inflammation, impaired fibroblast function, and imbalance of extracellular matrix deposition and remodeling, and delayed wound healing [9]. A longer duration of diabetes has been associated with a greater risk of impaired wound healing; consistent with this observation, duration of diabetes has been correlated with more profound diabetic neuropathy, increasingly compromised biomechanical properties of diabetic skin, and an increasingly delayed rate of endothelial progenitor cell proliferation. While the cytokines, chemokines, and cellular components of the wound healing response have been extensively studied, recent attention has focused upon the role that microRNAs (miRNAs) play in the impaired healing of diabetic wounds [3].

MiRNAs are a class of small, noncoding RNA molecules, 20-22 nucleotides long, that regulate gene expression at the posttranscriptional level [10]. Complementary binding of miRNAs to the 3'-untranslated region (UTR) of their target messenger RNA (mRNA) results in posttranscriptional repression and/or mRNA degradation, thereby regulating the expression of downstream targets [11]. MiRNA are thought to regulate over one-third of all physiologic processes, including regulation of cell cycle progression, apoptosis, cytokine transcription, cellular metabolic function, signal transduction, proliferation, and determination of cell fate [12, 13]. MicroRNAs are being investigated for their role as biomarkers, diagnostic tools, and therapies in a variety of disease states, including diabetes and numerous types of cancer [14, 15]. Key to the development of the diabetic phenotype is the dysregulation of the expression of miRNA that regulate inflammation, extracellular matrix composition, and angiogenesis. Here we discuss data that demonstrate correction of microRNA dysregulation expedites wound healing and reverses the diabetic phenotype in skin [16–18].
