Tannic acid as a bioactive polyphenol for hydrogel engineering in wound healing

Abstract Tannic acid (TA) is a widely available plant-derived polyphenol with a long history of use in the leather industry due to its strong affinity for collagen. This long-standing application stems from the ability of TA to form stable complexes with collagen and gelatin via multiple interactions, making it not only a natural tanning agent but also a valuable crosslinker in modern biomaterials. In recent years, TA has garnered increasing attention in wound healing applications because of its multifunctional bioactivities, including antibacterial, antioxidant, anti-inflammatory, and hemostatic effects. The abundant phenolic hydroxyl groups enable various covalent and noncovalent interactions (such as hydrogen bonding, metal coordination, π–π stacking, and oxidative coupling) with biomacromolecules and inorganic components, thereby enhancing the mechanical properties and biological functions of the hydrogel. This review summarizes the historical background and physicochemical properties of TA, introduces current hydrogel construction strategies (e.g., polymer blending and postfabrication immersion), and highlights the roles of TA in modulating the wound microenvironment by combating infection, scavenging reactive oxygen species, regulating inflammation, and promoting tissue regeneration. Advances in the use of TA-based hydrogels for treating acute, infected, and chronic wounds and other types of tissue injury are discussed. Furthermore, this review addresses the significant challenges—namely, stability, mechanistic understanding, and biosafety—in the clinical translation of TA-based hydrogels and discusses potential strategies for future development. Graphical Abstract