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

Abstract

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.

Beneficial Effects of Green Tea EGCG on Skin Wound Healing: A Comprehensive Review

“…Hydrogels are insoluble hydrophilic materials with high water content (70–90%) and a soft elastic property [ 26 ] which can be produced from synthetic polymers or natural macromolecule polymers. High-molecular polymers, e.g., poly (methacrylates) and polyvinyl pyrrolidine, are artificial polymers that are widely used, while polysaccharides (e.g., chitosan, hyaluronic acid, alginate and cellulose) and proteins (e.g., collagen, alginate and gelatin) are common natural hydrogels [ 12 ]. Hydrogels have been used for translational medicine and sealants with the advantages of better tissue adhesive character [ 19 , 27 ], rapid gelation and injectable properties [ 28 , 29 ] as well as good biocompatibility [ 30 ].…”

“…EGCG was conjugated with hyaluronic acids, and the conjugates further reacted with tyramine-conjugated hyaluronic acids through tyrosinase to form a crosslinked adhesive hydrogel [ 20 ]. A simplified one-pot synthesis method of EGCG–chitosan hydrogels were developed through enzyme-mediated cross-linking [ 12 ]. EGCG was copolymerized with 3-acrylamido phenyl boronic acid and acrylamide to form a hydrogel with adequate mechanical properties and tissue adhesiveness [ 31 ].…”

“…The in vivo study showed an EGCG-containing sandwiched dressing facilitated wound tissue regeneration and accelerated the healing process [ 36 ]. An accelerated skin regeneration was also observed in the treatment with EGCG–chitosan hydrogels [ 12 ]. EGCG exerted a blocking effect on the TGF-β1/Smad signal transduction in anaplastic thyroid carcinoma cells [ 73 ], suggesting its prospect of suppressing the formation of aberrant scars.…”

“…CD68, as an M1 phenotype marker [ 86 ], was downregulated at the protein level in the wound tissue of diabetes mellitus mice treated with AuEA compared to the vehicle control group [ 59 ]. Moreover, EGCG or EGCG-containing wound dressing suppressed the responses of immune cells such as monocytes and macrophages in an in vivo mouse skin full defect model [ 12 ].…”

“…Thus, topical application might be an ideal route to fully achieve the functionalities of EGCG, considering the avoidance of gastrointestinal digestion and less adverse effects on other organs. The potential application of EGCG to skin wound treatment has been investigated, and some positive results in vitro and in vivo have been achieved [ 12 , 13 , 14 , 15 ]. The effects of EGCG on wound healing are associated with the application form and the dosage of EGCG, study models and treatment methods.…”