Evolving spectrum of diabetic wound: Mechanistic insights and therapeutic targets

Abstract

Diabetes mellitus is a chronic metabolic disorder resulting in an increased blood glucose level and prolonged hyperglycemia, causes long term health conse-quences. Chronic wound is frequently occurring in diabetes patients due to compromised wound healing capability. Management of wounds in diabetic patients remains a clinical challenge despite many advancements in the field of science and technology. Increasing evidence indicates that alteration of the biochemical milieu resulting from alteration in inflammatory cytokines and matrix metalloproteinase, decrease in fibroblast and keratinocyte functioning, neuropathy, altered leukocyte functioning, infection, etc., plays a significant role in impaired wound healing in diabetic people. Apart from the current pharmacotherapy, different other approaches like the use of conventional drugs, antidiabetic medication, antibiotics, debridement, offloading, platelet-rich plasma, growth factor, oxygen therapy, negative pressure wound therapy, low-level laser, extracorporeal shock wave bioengineered substitute can be considered in the management of diabetic wounds. Drugs/therapeutic strategy that induce angiogenesis and collagen synthesis, inhibition of MMPs, reduction of oxidative stress, controlling hyperglycemia, increase growth factors, regulate inflammatory cytokines, cause NO induction, induce fibroblast and keratinocyte proliferation, control microbial infections are considered important in controlling diabetic wound. Further, medicinal plants and/or phytoconstituents also offer a viable alternative in the treatment of diabetic wound. The focus of the present review is to highlight the molecular and cellular mechanisms, and discuss the drug targets and treatment strategies involved in the diabetic wound.

Keywords: Diabetic Wound; Diabetic Foot Ulcer; Epigenetic mechanisms; Therapeutic agents; Molecular Targets; Phytoconstituents

Core Tip: This paper reviewed molecular pathways and epigenetic mechanisms involved in the pathogenesis of diabetic wounds. The role of microbiota, oxidative stress, inflammatory cytokines, and alteration in the factors involved in normal wound healing process was highlighted. Molecular targets of therapeutic agents, the role of phytochemicals was discussed. The efficacy of several pharmacotherapy, treatment strategies, and recent clinical trials aiming to improve the outcome of diabetic foot ulcers was reviewed.