Priyodarshi Sengupta*, Biplabendu Talukdar, Rajib Chakraborty, Niranjan Bhattacharya

Diabetic ulcers, especially foot ulcers, represent a significant clinical and socioeconomic burden, due to impaired wound healing driven by chronic inflammation. In contrast, reduced levels of IL-10 and TGF-β further exacerbate poor healing outcomes therefore highlighting the crucial interplay between pro and anti-inflammatory cytokines. Also, advanced glycation and lipoxidation end-products, oxidative stress and immune dysregulation amplify tissue injury and impair cellular defence mechanisms. In the formation of advanced protein glycosylation reactions, hyperglycaemia, along with oxygen-free radicals, is also a contributing factor to the non-healing of ulcers. Advanced glycation end products or AGE products, are implicated in various diabetic complications and inflammation. Another less characterized synthetic end product is advanced lipoxidation end product or ALE, which is implicated in the increased expression of cyclooxygenase-2, MCP-1, IL-6 and eight dysfunction. In fact, even keratinocytes, microvascular endothelial cells, excessive production of free oxygen radicals and NO are also involved in cytokine dysregulation and non-healing of diabetic ulcers. Together, these alterations result in chronic, non-resolving wounds characteristic of DFUs. Understanding these inflammatory mechanisms will help to shed light on the pathophysiology of impaired healing but also identifies potential biomarkers and therapeutic targets for improving DFU management. The following review highlights the complex interplay of pro- and anti-inflammatory cytokines, chemokines and growth factors that disrupt the normal wound-healing cascade in diabetic patients. High levels of TNF-α, IL-1β, IL-6, CRP and other mediators contribute to persistent low-grade inflammation, impaired fibroblast function, excessive extracellular matrix degradation and delayed angiogenesis.