Nanohydrogels for Diabetic Wound Healing: Mechanisms, Applications, and Future Perspectives

Diabetic wound healing remains a significant clinical challenge, characterized by persistent hyperglycemia, chronic inflammation, impaired angiogenesis, and recurrent infections. Traditional wound dressings often fail to address the complex pathological microenvironment of diabetic wounds. Nanohydrogels, particularly nanohybrid systems such as polyhedral oligomeric silsesquioxane (POSS)-based hydrogels, metal-organic framework (MOF) nanozyme hydrogels, and zinc-based polyoxometalate (Zn-POM) hydrogels, have emerged as advanced multifunctional platforms for diabetic wound repair. This review systematically summarizes the pathological mechanisms underlying diabetic wound chronicity and the material properties of nanohydrogels that enable targeted therapeutic interventions. We focus on the unique advantages of nanohybrid systems, including their high water retention, tunable mechanical properties, stimuli-responsiveness, and biocompatibility. Furthermore, we provide a detailed analysis of representative nanohybrid hydrogel applications, highlighting their antibacterial, anti-inflammatory, pro-angiogenic, and cell-promoting functions. Despite promising preclinical outcomes, challenges remain in large-scale production, mechanistic understanding, and clinical translation. Future directions include the development of intelligent, personalized nanohybrid systems and the integration of multi-omics approaches to elucidate their in vivo mechanisms. This review aims to provide a comprehensive and critical overview of nanohybrid hydrogels for diabetic wound healing, offering insights for researchers and clinicians in the field.