Engineering polyphenol composite hydrogels for accelerated tissue repair and regeneration

Natural polyphenols constitute a versatile chemical toolkit for hydrogel engineering due to their catechol, galloyl, and phenolic hydroxyl groups, which enable controllable hydrogen bonding, π–π stacking, metal coordination, and covalent cross-linking with polymers. These structure-defined interactions have been increasingly harnessed to design hydrogels with improved mechanical robustness, self-healing behavior, injectability, and tissue adhesiveness. This review classifies natural polyphenols based on their chemical structures and focuses on summarizing their biological activities, including anti-inflammatory, antioxidant, antibacterial effects, and modulation of the local immune microenvironment, along with the molecular mechanisms involved. Furthermore, it integrates specific therapeutic targets and reviews the latest research progress on polyphenol-based hydrogels in complex wound healing, neural repair, cartilage and bone regeneration, as well as oral and periodontal tissue repair. Finally, recent advancements in polyphenol-functionalized hydrogels are summarized and critically discussed, providing insights for the rational design and clinical translation of polyphenol-based hydrogels in tissue repair.