Fabrication of polyphenol-incorporated anti-inflammatory hydrogel via high-affinity enzymatic crosslinking for wet tissue adhesion

Su-Hwan Kim; Kyungmin Kim; Beom Seok Kim; Young-Hyeon An; Uk-Jae Lee; Sang-Hyuk Lee; Seunghyun L Kim; Byung-Gee Kim; Nathaniel S Hwang

doi:10.1016/j.biomaterials.2020.119905

Fabrication of polyphenol-incorporated anti-inflammatory hydrogel via high-affinity enzymatic crosslinking for wet tissue adhesion

Biomaterials. 2020 Feb 26:242:119905. doi: 10.1016/j.biomaterials.2020.119905. Online ahead of print.

Authors

Su-Hwan Kim¹, Kyungmin Kim², Beom Seok Kim², Young-Hyeon An², Uk-Jae Lee³, Sang-Hyuk Lee³, Seunghyun L Kim³, Byung-Gee Kim⁴, Nathaniel S Hwang⁵

Affiliations

¹ John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA; Institute of Engineering Research, Seoul National University, Republic of Korea; School of Chemical and Biological Engineering, Institute of Chemical Process, Seoul National University, Republic of Korea.
² School of Chemical and Biological Engineering, Institute of Chemical Process, Seoul National University, Republic of Korea.
³ School of Chemical and Biological Engineering, Institute of Chemical Process, Seoul National University, Republic of Korea; Interdisciplinary Program in Bioengineering, Seoul National University, Republic of Korea.
⁴ Institute of Engineering Research, Seoul National University, Republic of Korea; School of Chemical and Biological Engineering, Institute of Chemical Process, Seoul National University, Republic of Korea; Interdisciplinary Program in Bioengineering, Seoul National University, Republic of Korea; Institute of Bioengineering, Seoul National University, Republic of Korea; Institute of Molecular Biology and Genetics, Seoul National University, Republic of Korea.
⁵ Institute of Engineering Research, Seoul National University, Republic of Korea; School of Chemical and Biological Engineering, Institute of Chemical Process, Seoul National University, Republic of Korea; Interdisciplinary Program in Bioengineering, Seoul National University, Republic of Korea; Institute of Bioengineering, Seoul National University, Republic of Korea. Electronic address: nshwang@snu.ac.kr.

PMID: 32145505
DOI: 10.1016/j.biomaterials.2020.119905

Abstract

Epigallocatechin gallates (EGCGs), isolated from green tea, have intrinsic properties such as anti-oxidant, anti-inflammation, and radical scavenger effects. In this study, we report a tissue adhesive and anti-inflammatory hydrogel formed by high-affinity enzymatic crosslinking of polyphenolic EGCGs. A mixture of EGCG conjugated hyaluronic acids (HA_E) and tyramine conjugated hyaluronic acids (HA_T) was reacted with tyrosinase isolated from Streptomyces avermitillis (SA_Ty) to form that displayed fast enzyme kinetic to form a crosslinked adhesive hydrogel. A 1,2,3-trihydroxyphenyl group in EGCG displayed a high affinity to SA_Ty that allowed HA_E to be quickly oxidized and crosslinked with HA_T to form HA_T and HA_E mixed hydrogel (HA_TE). We then compared the HA_TE hydrogel with commercially available tissue adhesives, such as cyanoacrylate and fibrin glue. We report that the HA_TE exhibited the highest tissue adhesiveness both in wet and dry conditions. Furthermore, HA_TE successfully closed a skin wound and displayed insignificant host tissue responses. This demonstrates that polyphenol-incorporated anti-inflammatory hydrogel may provide a robust tissue adhesive platform for clinical applications.

Keywords: Adhesive; Anti-Inflammation; Polyphenol; Tissue sealant; Tyrosinase.