Polymeric Nanofiber Scaffolds for Diabetic Wound Healing: A Review

With the global diabetes epidemic, diabetic foot ulcers (DFUs) have become a major health burden, affecting approximately 18 million people worldwide each year, and account for about 80% of diabetes-related amputations. Five-year mortality among DFU patients approaches 30%, which is comparable to that of many malignancies. Yet despite standard wound care, only about 30%–40% of chronic DFUs achieve complete healing within 12 weeks. This persistent failure shows that conventional dressings remain passive supports. They do not counteract underlying pathologies such as ischemia, prolonged inflammation, and infection. Recent advances in polymeric nanofiber scaffolds, particularly electrospun matrices, provide bioactive wound dressings designed to overcome these limitations. By mimicking extracellular matrix architecture (ECM) and delivering therapeutic biomolecules, polymeric nanofiber scaffolds can promote tissue regeneration and angiogenesis. They also modulate the wound immune response and combat infection through embedded antimicrobial agents. Innovative scaffold architectures further enhance healing outcomes. Core–shell and multilayer nanofibers enable sequential or sustained release of multiple factors. Biomimetic “basketweave” fiber layouts improve cell alignment, neovascularization, and wound closure, and stimuli-responsive scaffolds release therapeutics in response to wound pH or oxidative stress. Preclinical diabetic wound models and early clinical trials show that these engineered scaffolds accelerate wound closure, increase re-epithelialization, and reduce chronic inflammation relative to standard care. Notably, a recent clinical trial in patients with DFU reported 74% wound closure by 12 weeks with an electrospun scaffold vs. 33% with conventional therapy. However, translational challenges persist, including stability, sterilization compatibility, and scalable manufacturing of nanofiber scaffolds. This review discusses these hurdles and highlights future directions, including the development of smart biosensor-integrated scaffolds for responsive drug delivery, personalized patient-specific dressings, and AI-assisted design of polymer nanofibers to further optimize DFU healing outcomes.