Hyaluronic acid (HA)-based biomaterials have demonstrated only limited in vivo stability as a result of rapid degradation by hyaluronidase and reactive oxidative species. The green tea catechin, (−)-epigallocatechin-3-O-gallate (EGCG), has received considerable attention because of its powerful antioxidant and enzyme-inhibitory activities. We describe here the synthesis of HA-EGCG conjugate using a thiol-mediated reaction and its use for the preparation of a long-lasting injectable hydrogel. HA-EGCG conjugates with tunable degrees of substitution were synthesized by the nucleophilic addition reaction between EGCG quinone and thiolated HA under mild conditions. Contrary to unmodified HA, the conjugates exhibited free radical scavenging and hyaluronidase-inhibitory activities. Peroxidase-catalyzed coupling reaction between EGCG moieties was employed to produce in situ forming HA-EGCG hydrogel with surprisingly high resistance to hyaluronidase-mediated degradation. When injected subcutaneously in mice, HA-EGCG hydrogel was retained much longer than HA-tyramine hydrogel with minimal inflammation.

中文翻译：

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硫醇介导的透明质酸-表没食子儿茶素-3 - O-加仑合物的合成，可形成具有自由基清除能力和抗降解性的可注射水凝胶。

由于透明质酸酶和反应性氧化物质的快速降解，基于透明质酸（HA）的生物材料仅表现出有限的体内稳定性。绿茶儿茶素（-）-epigallocatechin-3- O-gallate（EGCG）由于其强大的抗氧化剂和酶抑制活性而备受关注。我们在这里描述了使用硫醇介导的反应合成HA-EGCG缀合物及其在制备持久性可注射水凝胶中的用途。通过在温和条件下EGCG醌与硫醇化HA之间的亲核加成反应合成了具有可调取代度的HA-EGCG共轭物。与未修饰的HA相反，结合物表现出自由基清除和透明质酸酶抑制活性。EGCG部分之间的过氧化物酶催化的偶联反应用于产生原位形成的HA-EGCG水凝胶，该凝胶对透明质酸酶介导的降解具有令人惊讶的高抗性。当给小鼠皮下注射时，