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用于软骨组织工程的可注射原位形成聚(L-谷氨酸)水凝胶

Injectable in situ forming poly(l-glutamic acid) hydrogels for cartilage tissue engineering.

作者信息

Yan Shifeng, Zhang Xin, Zhang Kunxi, Di Hao, Feng Long, Li Guifei, Fang Jianjun, Cui Lei, Chen Xuesi, Yin Jingbo

机构信息

Department of Polymer Materials, Shanghai University, 333 Nanchen Road, Shanghai 200444, People's Republic of China.

出版信息

J Mater Chem B. 2016 Feb 7;4(5):947-961. doi: 10.1039/c5tb01488c. Epub 2016 Jan 11.

Abstract

Injectable, in situ forming hydrogels have exhibited many advantages in regenerative medicine. Herein, we present the novel design of poly(l-glutamic acid) injectable hydrogels via the self-crosslinking of adipic dihydrazide (ADH)-modified poly(l-glutamic acid) (PLGA-ADH) and aldehyde-modified poly(l-glutamic acid) (PLGA-CHO), and investigate their potential in cartilage tissue engineering. Both the hydrazide modification degree of PLGA-ADH and oxidation degree of PLGA-CHO can be adjusted by the amount of activators and sodium periodate, respectively. Experiments reveal that the solid content of the hydrogels, -NH/-CHO molar ratio, and oxidation degree of PLGA-CHO have a great effect on the gelation time, equilibrium swelling, mechanical properties, microscopic morphology, and in vitro degradation of the hydrogels. Encapsulation of rabbit chondrocytes within the hydrogels showed viability of the entrapped cells and cytocompatibility of the injectable hydrogels. A preliminary study exhibits injectability and rapid in vivo gel formation, as well as mechanical stability, cell ingrowth, and ectopic cartilage formation. These results suggest that the PLGA hydrogel has potential as an injectable cell delivery carrier for cartilage regeneration and could serve as a new biomaterial for tissue engineering.

摘要

可注射原位形成水凝胶在再生医学中已展现出诸多优势。在此,我们通过己二酸二酰肼(ADH)修饰的聚(L-谷氨酸)(PLGA-ADH)与醛修饰的聚(L-谷氨酸)(PLGA-CHO)的自交联,提出了聚(L-谷氨酸)可注射水凝胶的新颖设计,并研究了它们在软骨组织工程中的潜力。PLGA-ADH的酰肼修饰程度和PLGA-CHO的氧化程度可分别通过活化剂和高碘酸钠的用量进行调节。实验表明,水凝胶的固含量、-NH/-CHO摩尔比以及PLGA-CHO的氧化程度对水凝胶的凝胶化时间、平衡溶胀、力学性能、微观形态和体外降解有很大影响。将兔软骨细胞包封在水凝胶中显示出包封细胞的活力以及可注射水凝胶的细胞相容性。一项初步研究展示了其可注射性和在体内的快速凝胶形成,以及力学稳定性、细胞向内生长和异位软骨形成。这些结果表明,PLGA水凝胶有潜力作为用于软骨再生的可注射细胞递送载体,并可作为组织工程的新型生物材料。

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