Mechanistic insights of diabetic wound: Healing process, associated pathways and microRNA-based delivery systems

Wounds that represent one of the most critical complications can occur in individuals suffering from diabetes mellitus, and results in the need for hospitalisation and, in severe cases, require amputation. This condition is primarily characterized by infections, persistent inflammation, and delayed healing processes, which exacerbate the overall health of the patients. As per the standard mechanism, signalling pathways such as PI3K/AKT, HIF-1, TGF-β, Notch, Wnt/β-Cat, NF-κB, JAK/STAT, TLR, and Nrf2 play major roles in inflammatory, proliferative and remodelling phases of wound healing. However, dysregulation of the above pathways has been seen during the healing of diabetic wounds. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate the expression of various genes and signalling pathways which are associated with the process of wound healing. In the past few years, there has been a great deal of interest in the potential of miRNAs as biological agents in the management of a number of disorders. These miRNAs have been shown to modulate expression of genes involved in the healing process of wounds. There have been previous reviews pertaining to clinical trials examining miRNAs in several disorders, but only a few clinical studies have examined involvement of miRNAs in healing of wounds. Considering the therapeutic promise, there are several obstacles concerning their instabilities and inefficient delivery into the target cells. Therefore, this review is an attempt to discuss precise roles of signalling pathways and miRNAs in different phases of wound healing, and their aberrant regulation in diabetic wounds, particularly. It has also compiled a range of delivery mechanisms as well as an overview of the latest findings pertaining to miRNAs and associated delivery systems for improved healing of diabetic wounds.