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一种通过DA点击化学制备的、含pH敏感纳米颗粒的可注射透明质酸基复合水凝胶及其在生物医学中的应用

An Injectable Hyaluronic Acid-Based Composite Hydrogel by DA Click Chemistry With pH Sensitive Nanoparticle for Biomedical Application.

作者信息

Hu Xiaohong, Gao Ziyu, Tan Huaping, Wang Huiming, Mao Xincheng, Pang Juan

机构信息

School of Material Engineering, Jinling Institute of Technology, Nanjing, China.

Biomaterials for Organogenesis Laboratory, School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing, China.

出版信息

Front Chem. 2019 Jul 3;7:477. doi: 10.3389/fchem.2019.00477. eCollection 2019.

Abstract

Hydrogels with multifunctional properties attracted intensively attention in the field of tissue engineering because of their excellent performance. Also, object-oriented design had been supposed to an effective and efficient method for material design as cell scaffold in the field of tissue engineering. Therefore, a scaffold-oriented injectable composite hydrogel was constructed by two components. One was pH-sensitive bifunctional nanoparticles for growth factor delivery to improve biofunctionability of hydrogel scaffold. The other was Diels-alder click crosslinked hyaluronic acid hydrogel as matrix. pH dependent release behavior of nanoparticle component was confirmed by results. And, its bioactivity was verified by cell culture evaluation. In consideration of high-efficiency and effectiveness, low toxicity, controllability and reversibility, dynamic covalent and reversible Diels-alder click chemistry was used to design a HA hydrogel with two kinds of crosslinking points. The properties of hydrogel like gelation time and swelling ratio were influenced by pH value and polymer concentration. Composite hydrogel was formed by polymerization, which exhibited acceptable mechanical property as a scaffold for biomedical field. Lastly, evaluation from results of viability, DNA content and cell morphology confirmed that hydrogels could maintain cell activity and support cell growth. Compared with pure hydrogel, composite hydrogel possessed better properties.

摘要

具有多功能特性的水凝胶因其优异的性能在组织工程领域引起了广泛关注。此外,面向对象设计被认为是组织工程领域中作为细胞支架的材料设计的一种有效且高效的方法。因此,通过两种成分构建了一种面向支架的可注射复合水凝胶。一种是用于生长因子递送的pH敏感双功能纳米颗粒,以改善水凝胶支架的生物功能。另一种是作为基质的狄尔斯-阿尔德点击交联透明质酸水凝胶。结果证实了纳米颗粒成分的pH依赖性释放行为。并且,通过细胞培养评估验证了其生物活性。考虑到高效性、有效性、低毒性、可控性和可逆性,使用动态共价且可逆的狄尔斯-阿尔德点击化学设计了一种具有两种交联点的透明质酸水凝胶。水凝胶的性质如凝胶化时间和溶胀率受pH值和聚合物浓度的影响。复合水凝胶通过聚合形成,作为生物医学领域的支架表现出可接受的机械性能。最后,从活力、DNA含量和细胞形态结果的评估证实水凝胶可以维持细胞活性并支持细胞生长。与纯水凝胶相比,复合水凝胶具有更好的性能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17c0/6617958/7b3fc1d2285a/fchem-07-00477-g0011.jpg

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