Advances in diabetic foot ulcer management: a narrative review of novel antibiotics, nanotechnology, and regenerative therapeutics
9 affiliations
- 1Department of Pathology, College of Medicine, University of Hail
- 2Department of Family and Community Medicine, College of Medicine, University of Hail
- 3Department of Medicine, College of Medicine, University of Hail
- 4Department of Pharmacology, Medical Education Committee, College of Medicine, University of Hail
- 5Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University
- 6Health and Medical Research Center, King Khalid University
- 7Department of Surgery, College of Medicine, University of Hail
- 8Department of General Surgery, King Khalid Hospital
- 9Department of Microbiology, Hind Institute of Medical Sciences
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.
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BibTeX
@article{saleem2026advances,
title = {{Advances in diabetic foot ulcer management: a narrative review of novel antibiotics, nanotechnology, and regenerative therapeutics}},
author = {Mohd Saleem and Farida Habib Khan and Sumayyah Mohammad Almarshedy and Fahaad S. Alenazi and Hamad Alshetaiwi and Irfan Ahmad and Fauwaz Fahad Alrashid and Syed Muhammad. Ozair Ilyas and Abdulrahman Moussa Almuwaisa and Wael Nahi Alnomasi and Mohd Shahid Khan},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1882663},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1882663/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Advances in diabetic foot ulcer management: a narrative review of novel antibiotics, nanotechnology, and regenerative therapeutics
AU - Mohd Saleem
AU - Farida Habib Khan
AU - Sumayyah Mohammad Almarshedy
AU - Fahaad S. Alenazi
AU - Hamad Alshetaiwi
AU - Irfan Ahmad
AU - Fauwaz Fahad Alrashid
AU - Syed Muhammad. Ozair Ilyas
AU - Abdulrahman Moussa Almuwaisa
AU - Wael Nahi Alnomasi
AU - Mohd Shahid Khan
PY - 2026
DA - 2026/10/13
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1882663
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1882663/full
AB - 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.
SN - 1664-302X
ER -