Bioactive Compound-Integrated Metal Nanoparticles Promote Wound Repair in Diabetic Conditions: Evidence from an Animal Study.

A significant clinical challenge in diabetic wound healing was impaired healing dynamics, necessitating innovative therapeutic strategies. Naturally derived bioactive molecules like alkaloids, terpenoids, flavonoids and polyphenols had demonstrated antimicrobial, antioxidant, anti-inflammatory, angiogenic, and collagen-promoting activities, but their clinical application is limited by poor solubility, metabolic instability, and low bioavailability. Using metallic nanoparticles (gold, silver, zinc oxide and copper oxide) in nanotechnology offers a promising platform to overcome these barriers, serving both as therapeutic agents and as delivery vehicles that enhance stability, tissue penetration, and controlled release of bioactive compounds. Preclinical studies using rodent and large-animal diabetic wound models have provided mechanistic insights into the synergistic effects of bioactive compound-incorporated nanoformulations, showing improvements in angiogenesis, fibroblast proliferation, immune regulation, and oxidative stress modulation. This review consolidates recent advancements in nano-enabled bioactive formulations for diabetic wound healing, critically analyzes their mechanisms of action and physicochemical determinants, and highlights translational challenges and research gaps. Ultimately, the integration of phytochemicals with nanotechnology holds substantial promise for accelerating wound repair and advancing towards clinical application.