Combination therapy strategies for diabetic foot ulcers: synthesizing antibiotics, growth factors, and nanocarriers in modern wound management.

Diabetic foot ulcers (DFUs) are serious complications of diabetes, and consist of chronic wound healing, chronic biofilm infection, impaired angiogenesis, oxidized stress, and persistent inflammation. Standard treatments such as systemic antibiotics and growth factors have been found to be ineffective due to poor tissue penetration, degradation and antimicrobial resistance. The aim of this review is to critically analyze advanced strategies for combination therapy using antibiotics, growth factors and/or nanocarriers in order to better manage DFU. Literature was searched in PubMed, Scopus, Web of Science, and Google Scholar databases from January 2010 to March 2026 using keywords related to DFUs, antibiotics, growth factors, nanocarriers, biofilms, and wound healing. Combination nanotherapeutic systems exhibited potential to improve local drug delivery, disrupt biofilms, promote angiogenesis and support tissue regeneration. Stimuli-responsive and sequential-release platforms could enhance therapeutic precision by synchronizing antimicrobial and regenerative functions. Controlled release and modulation of the wound microenvironment are also enhanced by engineering scaffolds and multifunctional biomaterials. Yet the hurdles of biosafety, oxidative cytotoxicity, manufacturing scale-up, regulatory approval, and extended clinical duration remain significant obstacles to translation. Advanced multifunctional nanotherapeutics represent promising emerging strategies for precision-based DFU treatment and may improve infection control, tissue regeneration, and clinical healing outcomes.