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通过高亲和力酶交联制备用于湿组织粘连的含多酚抗炎水凝胶

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

作者信息

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

机构信息

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.

School of Chemical and Biological Engineering, Institute of Chemical Process, Seoul National University, Republic of Korea.

出版信息

Biomaterials. 2020 Jun;242:119905. doi: 10.1016/j.biomaterials.2020.119905. Epub 2020 Feb 26.

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

摘要

从绿茶中分离出的表没食子儿茶素没食子酸酯(EGCG)具有抗氧化、抗炎和自由基清除等内在特性。在本研究中,我们报道了一种通过多酚类EGCG的高亲和力酶交联形成的组织粘合剂和抗炎水凝胶。将EGCG共轭透明质酸(HA_E)和酪胺共轭透明质酸(HA_T)的混合物与从阿维链霉菌中分离出的酪氨酸酶(SA_Ty)反应,以形成具有快速酶动力学的交联粘合剂水凝胶。EGCG中的1,2,3-三羟基苯基对SA_Ty具有高亲和力,使得HA_E能够快速氧化并与HA_T交联,形成HA_T和HA_E混合水凝胶(HA_TE)。然后,我们将HA_TE水凝胶与市售的组织粘合剂,如氰基丙烯酸酯和纤维蛋白胶进行了比较。我们报道,HA_TE在湿态和干态条件下均表现出最高的组织粘附性。此外,HA_TE成功闭合了皮肤伤口,并且显示出微不足道的宿主组织反应。这表明掺入多酚的抗炎水凝胶可为临床应用提供一个强大的组织粘合剂平台。

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