Advances in diabetic foot ulcer management: a narrative review of novel antibiotics, nanotechnology, and regenerative therapeutics

Abstract

Diabetic foot ulcers (DFUs) are a major cause of hospitalization, chronic infection, and non-traumatic lower-limb amputation, imposing substantial clinical and economic burdens worldwide. Standard DFU management requires a multidisciplinary approach involving pressure offloading, regular debridement, infection control, metabolic optimisation, vascular assessment, and revascularisation when indicated. Offloading and sharp debridement reduce mechanical stress, remove devitalized tissue, disrupt biofilms, and support wound healing. Infected ulcers require appropriate microbiological assessment and culture-directed antimicrobial therapy, particularly when multidrug-resistant (MDR) pathogens are present. Biofilm formation is an important feature of chronic DFUs and is associated with persistent infection, delayed healing, and treatment failure. Biofilm-associated antimicrobial tolerance results from factors including reduced antimicrobial penetration, metabolic dormancy, altered growth states, and phenotypic heterogeneity, and should be distinguished from genetically mediated antimicrobial resistance caused by acquired or chromosomal genetic determinants. Although biofilm-associated tolerance does not necessarily involve genetic resistance, persistent biofilm infection may facilitate the selection and persistence of resistant subpopulations. Both Gram-positive and Gram-negative organisms can form biofilms in DFUs. Novel antibiotics, including oxazolidinones, lipoglycopeptides, lipopeptides, and advanced β-lactam/β-lactamase inhibitor combinations, may provide options for selected difficult to treat infections, although evidence varies among agents and clinical settings. Adjunctive wound-care strategies, including appropriate dressings and negative-pressure wound therapy, may support wound-bed preparation and healing in selected cases. Emerging approaches such as nanoparticle-based delivery systems, hydrogels, nanofibrous scaffolds, stem-cell and exosome therapies, gene and RNA-based strategies, and oxygen-releasing biomaterials have shown potential in preclinical and early clinical studies. However, their clinical effectiveness, safety, reproducibility, scalability, and regulatory approval and clinical translation remain incompletely established. Integrating evidence-based standard care with appropriate antimicrobial therapy and carefully evaluated emerging technologies may facilitate individualized management of complex DFUs.