Enzyme-mediated one-pot synthesis of hydrogel with the polyphenol cross-linker for skin regeneration.

Polyphenols can trigger immunity that activates intracellular anti-inflammatory signaling and prevents external infections. In this study, we report the fabrication of chitosan-based hydrogels with epigallocatechin gallate (EGCG) using enzyme-mediated one-pot synthesis. The tyrosinase-mediated oxidative reaction of the phenolic rings of EGCG with the primary amines on chitosan results in stable EGCG-chitosan hydrogels. The EGCG concentrations contributed to the cross-linking density and physical properties of EGCG-chitosan hydrogels. Furthermore, EGCG-chitosan hydrogels maintained intrinsic properties such as antibacterial and antioxidant effects. When endotoxin-activated RAW 264.7 macrophage cells were cultured with EGCG-chitosan hydrogels, the hydrogels reduced the inflammatory response of the RAW 264.7 cells. Furthermore, subcutaneous implantation of EGCG-chitosan hydrogels reduced endogenous macrophage and monocyte activation. When the EGCG-chitosan hydrogels were applied to a full-skin defect wound, they facilitated skin regeneration. Our study demonstrates that the one-pot synthesized EGCG-chitosan hydrogels can be applied in broad tissue regeneration applications that require immune modulation.