Current therapeutic strategies in the management of diabetic foot ulcers

Diabetic foot ulcer (DFU) is a chronic and predominantly microvascular and neuropathic complication in more severe or chronic cases of diabetes mellitus. It is characterized by chronic nonhealing wounds, vascular impairment, and delayed healing process, leading to severe complications, limb amputations, and increased mortality. With an annual incidence rate of approximately 2%, DFU poses a significant global healthcare and economic burden. Despite its prevalence, current treatment options remain limited, necessitating the urgent need for a deeper understanding of the underlying molecular pathways or mechanisms to develop effective therapeutic strategies. Present work is emphasized on molecular mechanisms involved in pathogenesis of DFU and current and emerging therapeutic interventions for the treatment of DFU. Due to its high prevalence, multifaceted pathophysiology, and significant healthcare and economic burden, a thorough understanding of molecular pathways underlying DFU is essential to develop precise therapeutic interventions to improve clinical outcome and reduce the healthcare burden associated with DFU. Several therapeutic interventions have been utilized, like modulators of key signaling pathways (Wnt/β-catenin, PI3K/Akt/mTOR, JAK/STAT, and Notch), repurposed pharmacological agents (e.g. metformin, colchicine, deferoxamine, and lithium carbonate), and advanced local treatments such as bioactive hydrogels and next-generation dressings. Furthermore, regenerative approaches like gene therapy, stem cell transplantation, therapeutic peptides, and 3D-bioprinted adipose tissue constructs provide a promising strategy for restoring tissue integrity and promoting healing.