Therapeutic Challenges in the Management of Diabetic Foot Ulcers: A Critical Review on Current and Emerging Treatment strategies

Mohammed Tameem S, Beny Baby, Natasha Soibam, Pragathi GS, B.S Nishal, Debasri Mukherjee

Diabetic foot ulcers (DFUs) remain one of the most severe and costly complications of diabetes mellitus, contributing substantially to morbidity, mortality, and lower-limb amputations worldwide. The pathogenesis of DFUs is multifactorial, involving peripheral neuropathy, ischemia, immune dysfunction, persistent inflammation, and microbial biofilm formation, all of which disrupt the normal wound-healing cascade. Although conventional management strategies—such as systemic antibiotics, debridement, offloading, and moist wound dressings—form the cornerstone of DFU care, their clinical effectiveness is often limited by antimicrobial resistance, poor patient adherence, delayed healing, and high recurrence rates. These limitations highlight the need for therapeutic approaches that address both infection control and the underlying pathophysiological abnormalities of diabetic wounds.
Recent advances in biomaterial science have led to the development of innovative wound care strategies, including nanofiber-based dressings, hydrogel systems, growth factor delivery platforms, and cell- or exosome-loaded scaffolds. These emerging technologies aim to modulate the wound microenvironment, enhance angiogenesis, provide controlled drug release, and promote tissue regeneration. However, despite encouraging preclinical outcomes, challenges related to biological instability, mechanical durability, scalability, safety, and regulatory approval continue to impede clinical translation. This review critically evaluates the global burden, pathophysiological mechanisms, and current therapeutic limitations in DFU management, while systematically discussing emerging biomaterial-based wound care strategies. By synthesizing existing evidence, this article underscores the need for clinically translatable, multifunctional wound dressings supported by well-designed clinical trials to improve long-term outcomes in patients with diabetic foot ulcers.

Keywords: Diabetic foot ulcer; Diabetes mellitus; Chronic wound healing; Peripheral neuropathy; Peripheral arterial disease; Biofilm formation; Antimicrobial resistance; Debridement; Offloading techniques; Advanced wound dressings; Biomaterials; Nanofibers; Electrospinning; Core–shell nanofibers; Drug delivery systems; Hydrogels; Composite hydrogels; Angiogenesis; Tissue regeneration.