Regulatory effects of natural polysaccharides on skin wound repair through modulation of immune-microbiome interactions.

Chronic non-healing wounds pose a significant clinical challenge, driven by dysregulation of the "inflammation-immune-microbiome" triad. Traditional "debridement-anti-infection-coverage" approaches fail to break the vicious cycle of dysbiosis and immune dysfunction. Leveraging structural diversity and bioactivity, natural polysaccharides provide a versatile platform for multi-targeted intervention. This review systematically explores the mechanisms through which polysaccharides modulate the wound immune microenvironment, restructure microbial communities, and facilitate barrier repair. This interaction enables precise regulation of macrophage polarization, particularly the promotion of the M2 phenotype, as well as neutrophil function and adaptive immunity, thereby alleviating chronic inflammation. Moreover, polysaccharides utilize a variety of mechanisms to impact the microbiome, including direct antimicrobial effects through electrostatic interactions and prebiotic support that promotes the colonization and metabolism of beneficial bacteria. This review also explores advancements in intelligent delivery systems, such as microenvironment-responsive hydrogels, discusses challenges in clinical translation, and considers future directions that incorporate single-cell multi-omics, microbiota-based personalization, organ-on-a-chip models, and phage-polysaccharide synergistic therapies. This work offers a theoretical foundation and translational perspective for the development of next-generation polysaccharide-based strategies for chronic wound management.