Progressive Hydrogel Applications in Diabetic Foot Ulcer Management: Phase-Dependent Healing Strategies

Diabetes is emerging as a significant health and societal concern globally, impacting both young and old populations. In individuals with diabetic foot ulcers (DFUs), the wound healing process is hindered due to abnormal glucose metabolism and chronic inflammation. Minor injuries, blisters, or pressure sores can develop into chronic ulcers, which, if left untreated, may lead to serious infections, tissue necrosis, and eventual amputation. Current management techniques include debridement, wound dressing, oxygen therapy, antibiotic therapy, topical application of antibiotics, and surgical skin grafting, which are used to manage diabetic wounds and foot ulcers. This review focuses on a hydrogel-based strategy for phase-wise targeting of DFUs, addressing sequential stages of diabetic wound healing: hemostasis, infection, inflammation, and proliferative/remodeling phases. Hydrogels have emerged as a promising wound care solution due to their unique properties in providing a suitable wound-healing microenvironment. We explore natural polymers, including hyaluronic acid, chitosan, cellulose derivatives, and synthetic polymers such as poly (ethylene glycol), poly (acrylic acid), poly (2-hydroxyethyl methacrylate, and poly (acrylamide), emphasizing their role in hydrogel fabrication to manage DFU through phase-dependent strategies. Recent innovations, including self-healing hydrogels, stimuli-responsive hydrogels, nanocomposite hydrogels, bioactive hydrogels, and 3D-printed hydrogels, demonstrate enhanced therapeutic potential, improving patient outcomes. This review further discusses the applicability of various hydrogels to each phase of wound healing in DFU treatment, highlighting their potential to advance diabetic wound care through targeted, phase-specific interventions.