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可生物降解透明质酸水凝胶通过水性 Diels-Alder 化学控制地塞米松释放用于脂肪组织工程。

Biodegradable hyaluronic acid hydrogels to control release of dexamethasone through aqueous Diels-Alder chemistry for adipose tissue engineering.

机构信息

School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing, China.

School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing, China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2015 Nov 1;56:311-7. doi: 10.1016/j.msec.2015.04.004. Epub 2015 Apr 15.

DOI:10.1016/j.msec.2015.04.004
PMID:26249595
Abstract

A robust synthetic strategy of biopolymer-based hydrogels has been developed where hyaluronic acid derivatives reacted through aqueous Diels-Alder chemistry without the involvement of chemical catalysts, allowing for control and sustain release of dexamethasone. To conjugate the hydrogel, furan and maleimide functionalized hyaluronic acid were synthesized, respectively, as well as furan functionalized dexamethasone, for the covalent immobilization. Chemical structure, gelation time, morphologies, swelling kinetics, weight loss, compressive modulus and dexamethasone release of the hydrogel system in PBS at 37°C were studied. The results demonstrated that the aqueous Diels-Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for hydrogel conjugation and covalent immobilization of dexamethasone. Cell culture results showed that the dexamethasone immobilized hydrogel was noncytotoxic and preserved proliferation of entrapped human adipose-derived stem cells. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gel scaffolds with ideal structures for adipose tissue engineering, which provides a competitive alternative to conventional conjugation techniques such as copper mediated click chemistry.

摘要

已经开发出一种基于生物聚合物的水凝胶的稳健合成策略,其中透明质酸衍生物通过水相 Diels-Alder 化学反应进行反应,而不涉及化学催化剂,从而可以控制和持续释放地塞米松。为了使水凝胶发生共轭,分别合成了呋喃和马来酰亚胺功能化的透明质酸,以及呋喃功能化的地塞米松,用于共价固定化。在 37°C 的 PBS 中研究了水凝胶体系的化学结构、凝胶时间、形态、溶胀动力学、失重、压缩模量和地塞米松释放。结果表明,水相 Diels-Alder 化学提供了一种极其选择性的反应,并且对于水凝胶的共轭和地塞米松的共价固定化具有高效率。细胞培养结果表明,固定有地塞米松的水凝胶无细胞毒性,并保持了包埋的人脂肪来源干细胞的增殖。这种合成方法独特地允许直接制造具有用于脂肪组织工程的理想结构的生物功能化凝胶支架,这为传统的共轭技术(例如铜介导的点击化学)提供了一种有竞争力的替代方法。

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