Therapeutic Effect of Silver Nanoparticles on Wet Gangrene and Diabetic Foot

Abstract

Background:
 Diabetic foot ulcers (DFUs) and wet gangrene are among the most serious complications of diabetes, often leading to infection, prolonged hospitalizations, and amputation. Traditional wound management strategies have limited efficacy due to microbial resistance, impaired healing, and chronic inflammation. Silver nanoparticles (AgNPs) have gained attention as a novel therapeutic agent because of their strong antimicrobial properties and potential to accelerate wound repair.
Objectives: To systematically review the therapeutic effects of silver nanoparticles in the treatment of diabetic foot ulcers and wet gangrene, focusing on mechanisms of action, clinical efficacy, safety, and formulation strategies.
Methods: Following PRISMA guidelines, a comprehensive literature search was conducted across PubMed, Scopus, and Web of Science, including all study types (clinical, in vivo, in vitro, and preclinical) that evaluated AgNP-based therapies for DFUs or gangrene. Studies were screened for relevance, and data were extracted on healing rates, infection clearance, adverse events, and formulation approaches.
Results: A total of 35 studies met the inclusion criteria, including randomized controlled trials, observational studies, and experimental models. Clinical evidence indicates that AgNP dressings significantly improve healing rates and reduce time to closure compared with standard wound dressings, although some meta-analyses show mixed results. Preclinical studies demonstrate that AgNPs accelerate epithelialization, collagen deposition, and angiogenesis, while reducing bacterial burden. Mechanistically, AgNPs disrupt microbial membranes, generate reactive oxygen species, and inhibit biofilm formation, while simultaneously stimulating keratinocyte and fibroblast proliferation and modulating inflammation. Safety analyses suggest that AgNPs can be cytotoxic at high concentrations; however, when embedded in hydrogels, nanofibers, or controlled-release matrices, they exhibit good biocompatibility.
Conclusions:
 Silver nanoparticles represent a promising adjunctive therapy for diabetic foot ulcers and wet gangrene due to their dual antimicrobial and wound-healing properties. Their efficacy is enhanced when incorporated into advanced dressings or combined with growth factors. Despite encouraging findings, variability in outcomes highlights the need for larger, standardized, and long-term clinical trials. Careful formulation and dosing are essential to minimize toxicity while maximizing therapeutic benefits.