Natural Bioactive Compound-Integrated Nanomaterials for Diabetic Wound Healing: Synergistic Effects, Multifunctional Designs, and Challenges

Diabetic wounds, as one of the most challenging complications of diabetes, exhibit impaired healing due to hyperglycemia, infection, vascular damage, microvascular deficits, dysregulated immune responses, and neuropathy. Conventional treatments are often limited by low drug bioavailability, transient therapeutic effects, and insufficient synergy across multiple pathways. Natural bioactive compounds are potential alternatives due to their multifunctional properties, including antioxidant, antimicrobial, and proangiogenic activities; however, their application is constrained by poor water solubility and rapid metabolism. Their integration with natural or synthetic nanovehicles significantly enhances stability, targeting, and controlled-release capabilities, while enhancing synergistic antimicrobial, immunomodulatory, and pro-repair functions. This review systematically catalogs the application of nanomaterial-loaded biomolecules, focuses on innovative progress in plant-based and animal-derived nanosystems, and further elucidates the multimodal therapeutic potential of synthetic-natural hybrid nanosystems. By synthesizing cutting-edge research, we also summarize advantageous features, development prospects, and existing challenges from the three dimensions of mechanistic evidence, preclinical validation, and current nanodelivery platforms, and propose a framework for grading application potential to provide a theoretical basis and strategic guidance for the rational design and clinical translation of future nanomedicines.