Enhancement of bio-stability and mechanical properties of hyaluronic acid hydrogels by tannic acid treatment

Hyaluronic acid (HA) has been widely investigated because of its excellent biocompatibility and its ability to form hydrogels with various chemical modifications. However, HA hydrogels undergo rapid degradation and exhibit poor mechanical stability under physiological conditions. Tannic acid (TA), a naturally occurring polyphenol found in plants and fruits, has recently attracted interest as a crosslinking agent because of its abundant hydroxyl groups. In this study, we prepared HA hydrogels chemically crosslinked by polyethylene glycol diglycidyl ether (PEGDE) and treated with TA in an attempt to enhance the physical properties of HA hydrogels. TA acts as a physical crosslinker owing to the strong hydrogen bonding between TA and PEGDE, resulting in improved mechanical properties that support both cell attachment and proliferation without any sign of cytotoxicity. The enzymatic stability of the HA-TA hydrogels was significantly enhanced with the addition of TA, which was attributed to the hyaluronidase inhibition activity of TA. Additionally, the antioxidant potential of TA resulted in good resistance to degradation by reactive oxygen species, which can be generated in human tissues.