Immunomodulatory and anti-oxidant mechanisms of plant-derived bioactive scaffolds in diabetic wound healing: Molecular pathways and therapeutic implications

Diabetic wound healing remains challenging due to persistent inflammation, oxidative stress, and impaired angiogenesis. Plant-derived bioactive scaffolds address multiple pathophysiological mechanisms simultaneously through inherent immunomodulatory and anti-oxidant properties. This review critically analyzes recent advances in plant-derived scaffolds for diabetic wound healing, focusing on molecular mechanisms. A systematic literature search was conducted in PubMed, Scopus, and Web of Science using terms such as “plant-derived scaffolds,” “decellularized scaffolds,” “diabetic wound healing,” “immunomodulation,” “anti-oxidant,” and “angiogenesis.” Studies published primarily between ۲۰۱۹ and ۲۰۲۶ that reported in vitro, in vivo, or ex vivo data on plant scaffold performance in diabetic wound models were prioritized; mechanistically relevant phytochemical studies were included where direct scaffold-level evidence was limited. The analysis emphasizes immunomodulatory, anti-oxidant, and angiogenic effects in experimental models. Plant-derived scaffolds from kelp, spinach, pomelo peel, walnut leaves, and mushrooms demonstrate therapeutic potential through multiple mechanisms. They promote macrophage polarization from pro-inflammatory M۱ to regenerative M۲ phenotypes, reduce reactive oxygen species via polyphenolic and flavonoid compounds, and enhance angiogenesis through VEGF up-regulation. Bioactive components, including fucoidan, gallic acid, carotenoids, and p-coumaric acid, reduce pro-inflammatory cytokines, enhance collagen deposition, and accelerate wound closure, exceeding ۹۰% by day ۱۴ in diabetic animal models, compared with approximately ۷۰% in untreated controls. Plant-derived bioactive scaffolds represent a paradigm shift in diabetic wound management by simultaneously targeting inflammation, oxidative stress, and impaired regeneration through naturally occurring bioactive compounds while preserving extracellular matrix architecture.

کلیدواژه ها:

Anti-oxidant mechanisms ، Bioactive compounds ، Diabetic wound healing ، Immunomodulation ، Macrophage polarization ، Plant-derived scaffolds