Multifunctional nanobiocomposite hydrogels for diabetic wound healing: Synergistic mechanisms, design principles, and...

Persistent inflammation, polymicrobial biofilm colonization, and impaired re-epithelialization characterize the chronic and treatment-resistant nature of diabetic wounds. Conventional treatment strategies often fail to adequately address the multifactorial pathophysiological mechanisms underlying these lesions. This review examines the biological functions, key components, and design principles of multifunctional hydrogel nanobiocomposites for diabetic wound healing. These hybrid systems combine natural biopolymers with functional nanoparticles specifically engineered for diabetic wound management. Such nanobiocomposite hydrogels provide an integrated platform capable of simultaneously controlling infection, modulating inflammation, and promoting tissue regeneration. Furthermore, the incorporation of bioactive agents, such as peptides and polyphenols, together with metallic nanoparticles, plays a critical role in enhancing therapeutic efficacy. Finally, this review discusses the major challenges associated with the clinical translation of these systems, including regulatory considerations, standardization, and large-scale manufacturing requirements, while delineating an actionable roadmap for their clinical integration.