Regenerative polymer-based modalities for diabetic foot ulcers: From material design to clinical translation

Diabetic foot ulcers (DFUs) cause one amputation every 20 s globally, driven by ischemia, dysregulated growth factors, recalcitrant biofilms, and oxidative stress that render conventional therapies ineffective. This review examines smart polymer dressings that actively sense pathological cues and respond with spatiotemporal precision. Natural polymers (chitosan, collagen, hyaluronic acid) provide biochemical signals for cell recruitment and angiogenesis, while synthetic polymers (Polylactic glycolic acid, Polycaprolactone, Polyethylene glycol) enable controlled degradation and drug release. Hybrid systems include glucose-responsive hydrogels, VEGF-loaded nanofibers for hypoxic zones, and microneedles that disrupt biofilms while delivering antimicrobials. In preclinical testing, these advanced dressings possess the capacity to achieve total wound closure in diabetic animal models. However, clinical translation is hindered by GMP manufacturing challenges, regulatory complexity, and cost barriers. This review analyses the state-of-the-art polymer design and engineering transforming passive dressings into active therapeutics and identifies critical gaps between laboratory breakthroughs and clinical implementation.