**5. Future directions**

While we have presented data on the correction of miRNA dysregulation in a diabetic murine model, future directions include extending these explorations to *in vitro* and *in vivo* human models in order to examine the clinical applicability of treating diabetic wounds with either MSCs or SDF‐1α, while also investigating how the duration of diabetes impacts miRNA dysregulation in human skin. Furthermore, in no way is the miRNA dysregulation document‐ ed in diabetes limited to miR‐146a, miR‐29a, and miR‐15b [14, 15, 39]. Numerous families of miRNA are known to be integral to the wound healing process, and we have only touched on a few of the key regulators. In addition to further evaluating the role these additional miRNA play in regulating the diabetic wound healing response, future directions in this field will likely delve into efforts to make autologous MSC treatment safe and economically feasible, the viability of gene therapy, nanoparticle technology, and improved biomaterials [41, 50, 51]. In addition to regulating protein gene expression, gene therapy could be utilized to upregulate beneficial miRNA expression or downregulate detrimental miRNA expression [39].

The burden of disease attributable to diabetic wounds is projected to intensify as the prevalence of diabetes increases worldwide. As detailed here, patients with diabetes suffer from impaired wound healing, with significant dysregulation at nearly every stage of the wound healing response [2]. This diabetic wound healing phenotype is characterized by decreased angiogen‐ esis, impaired leukocyte migration, decreased growth factor production, sustained inflamma‐ tion, impaired fibroblast function, imbalance of extracellular matrix deposition and remodeling, and delayed wound healing [9]. Central to the development of this diabetic phenotype is the dysregulation of miRNA that regulate inflammation (miR‐146a), extracellular matrix composition (miR‐29a), and angiogenesis (miR‐15b). We have demonstrated that correction of this microRNA dysregulation through treatment with MSCs expedites wound healing and reverses the diabetic phenotype in skin [16–18], and preliminary results suggest a similar effect following treatment with SDF‐1α. Understanding the role that miRNA play in the regulation of wound healing, as well as the numerous ways miRNA are dysregulated in the diabetic state, will be imperative as we strive to develop more effective wound care technologies in the future.
