Stimuli-Responsive Nanocomposite Hydrogels for Diabetic Foot Ulcer Management: Microenvironment Modulation and Therapeutic Synergy

DOI: https://doi.org/10.62517/jmhs.202505402

Author(s)

Lin Li#,*,Wan Yang#, Mengkun Li#, Yantiao Yang, Tiantian Wei, Yu Liu

Affiliation(s)

School of Life Sciences, Zhengzhou Normal University, Zhengzhou, Henan, China #They contributed equally s to this work. *Corresponding Author

Abstract

Diabetic foot ulcer (DFU) is a debilitating complication of diabetes mellitus, featuring chronic non-healing wounds, recurrent infections, and a high risk of lower-limb amputation. Its multifactorial pathogenesis involves hyperglycemia-induced immune dysfunction, impaired neutrophil and macrophage activity, and persistent activation of inflammatory pathways such as NF-κB, while a wound microenvironment rich in reactive oxygen species, pathogenic colonization, and chronic inflammation severely limits conventional therapies. Nanocomposite hydrogels offer a promising multifunctional platform for DFU management, as nanomaterial incorporation enhances mechanical strength, self-healing, adhesion under moist conditions, and stimuli responsiveness. Bioactive functionalization enables synergistic antibacterial, antioxidant, and anti-inflammatory effects, with controlled drug release and modulation of the wound microenvironment. Formulations containing silver nanoparticles, curcumin, tannic acid, honey-derived components, exosomes, or anti-inflammatory drugs have demonstrated accelerated tissue repair in preclinical studies. Continued multidisciplinary advances in design, bioactivity optimization, and in vivo evaluation may expedite clinical translation and improve patient outcomes while reducing amputation risk.

Keywords

Diabetic Foot Ulcer; Nanocomposite Hydrogel; Pathogenesis; Wound Healing; Antibacterial; Antioxidant; Anti-Inflammatory

References

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