Glucose Epimerization‐Modulated Phytochemicals Constructing Carrier‐Free Hydrogel for Regulation of Macrophage Phenotype to Promote Wound Healing

Abstract The self‐assembly of phytochemicals with multiple chiral centers is receiving significant attention for its potential in biomedical applications. However, the impact of single chiral center epimerization on molecular self‐assembly remains unexplored. Herein, the self‐assembly behavior and bioactivities of 1,2,3,4,6‐penta‐O‐galloyl‐α‐D‐glucose (α‐D‐PGG) and 1,2,3,4,6‐penta‐O‐galloyl‐β‐D‐glucose (β‐D‐PGG) is examined, a pair of natural ellagitannins abundant in plants. Interestingly, β‐D‐PGG formed a hydrogel without modification, while α‐D‐PGG does not. This occurred due to the balanced distribution of aromatic rings and phenolic hydroxyl groups in β‐D‐PGG, facilitating self‐assembly via hydrogen bonding and π–π stacking into nanofibers. In contrast, α‐D‐PGG's self‐assembly is inhibited by steric hindrance. Notably, β‐D‐PGG hydrogel demonstrated exceptional antibacterial activity and by regulating macrophage polarization toward the M2 phenotype, thereby reducing inflammation. This study not only reveals the distinct self‐assembly behaviors of glucose derivatives but also offers new insights into their potential in biomedical applications, such as wound healing.