Mechanisms of Impaired Wound Healing in Type 2 Diabetes: The Role of Epigenetic Factors

Despite decades of research, impaired extremity wound healing in type 2 diabetes remains a significant driver of patient morbidity, mortality, and health care costs. Advances in surgical and medical therapies, including the advent of endovascular interventions for peripheral artery disease and topical therapies developed to promote wound healing, have not reduced the frequency of lower leg amputations for nonhealing wounds in type 2 diabetes. This brief report is aimed at reviewing the roles of various cell types in tissue repair and summarizing the known dysfunctions of these cell types in diabetic foot ulcers. Recent advances in our understanding of the epigenetic regulation in immune cells identified to be altered in type 2 diabetes are summarized, and particular attention is paid to the developing research defining the epigenetic regulation of structural cells, including keratinocytes, fibroblasts, and endothelial cells. Gaps in knowledge are highlighted, and potential future directions are suggested based on the current state of the field.