This review summarizes the recent advances in biointerfacial engineering using polyphenolic platforms, highlighting the relationship between material properties and cell biology regulation via cell–material contact and non-contact modes.

Robust and multifunctional polyphenolic hydrogels have been well acknowledged as promising biomaterial candidates due to their various fascinating properties in regulating cell biology. However, the construction of these hydrogels commonly needs multistep fabrication and a sophisticated gelation process. The typical phenol-aldehyde condensation is a facial and in situ reaction for industrial resin construction; however, its application in hydrogel fabrication is seldom reported. In this study, we reported the feasibility and modularity of this strategy for in situ fabricating various kinds of robust and multifunctional natural polyphenolic hydrogels using natural polyphenol (extracts) and formaldehyde. The physicochemical characterization results demonstrated that the chemical structure (e.g., phenolic hydroxyl groups) of polyphenol molecules could be well maintained after the gelation process, allowing as-prepared hydrogels to inherit the merits of polyphenol molecules, such as good UV shielding, radical scavenging, antibacterial properties, and so forth, as demonstrated by in vitro data. The in vitro and in vivo cellular and animal results further confirmed that the as-prepared hydrogels were able to perform a skin protection and repair role, as demonstrated in UV protection and wound healing models. Collectively, this strategy could allow natural polyphenols as both structural and functional synthons toward more types of robust hydrogels for a wide range of biomedical applications.