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一种通过生物正交应变促进叠氮化物-炔烃环加成点击化学制备的可注射且快速降解的聚乙二醇水凝胶。

An injectable and fast-degradable poly(ethylene glycol) hydrogel fabricated via bioorthogonal strain-promoted azide-alkyne cycloaddition click chemistry.

作者信息

Jiang Huafang, Qin Siyong, Dong Hui, Lei Qi, Su Xin, Zhuo Renxi, Zhong Zhenlin

机构信息

Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.

出版信息

Soft Matter. 2015 Aug 14;11(30):6029-36. doi: 10.1039/c5sm00508f. Epub 2015 Jul 1.

DOI:10.1039/c5sm00508f
PMID:26132425
Abstract

Biocompatible and degradable injectable materials prepared via bioorthogonal reactions are highly promising for biomedical applications because they can be formed in situ and administered in a minimally invasive way. In this work, a PEG-based injectable hydrogel was fabricated via a copper-free, strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry. Azide and cyclooctyne moieties on the PEG backbones underwent a rapid click reaction to trigger the formation of the hydrogel within several minutes. Resulting from the introduction of ester groups into the cross-linked network, the hydrogel presented pH-dependent hydrolysis and biological fast degradability. Good biocompatibility of the hydrogel was verified by in vitro cytotoxicity assay and in vivo studies. The hydrogel formed in situ after subcutaneously injecting the gel precursors into Kungming (KM) mice. The implanted hydrogel caused a mild inflammatory response in vivo, and the surrounding tissues fully recovered a week after the injection. The injectable and fast-degradable hydrogel fabricated by the bioorthogonal click reaction may be useful as biomaterials such as embolic agents for interventional therapy.

摘要

通过生物正交反应制备的生物相容性和可降解的可注射材料在生物医学应用中极具前景,因为它们可以原位形成并以微创方式给药。在这项工作中,通过无铜的应变促进叠氮化物-炔烃环加成(SPAAC)点击化学制备了一种基于聚乙二醇(PEG)的可注射水凝胶。PEG主链上的叠氮化物和环辛炔部分发生快速点击反应,在几分钟内引发水凝胶的形成。由于酯基引入交联网络,该水凝胶呈现出pH依赖性水解和生物快速降解性。通过体外细胞毒性试验和体内研究验证了水凝胶良好的生物相容性。将凝胶前体皮下注射到昆明(KM)小鼠体内后原位形成水凝胶。植入的水凝胶在体内引起轻度炎症反应,注射一周后周围组织完全恢复。通过生物正交点击反应制备的可注射且快速降解的水凝胶可用作介入治疗的栓塞剂等生物材料。

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