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用于软骨组织工程的新型可注射多孔聚(γ-苄基-L-谷氨酸)微球:制备与评价

Novel injectable porous poly(γ-benzyl-l-glutamate) microspheres for cartilage tissue engineering: preparation and evaluation.

作者信息

Fang Jianjun, Yong Qi, Zhang Kunxi, Sun Wentao, Yan Shifeng, Cui Lei, Yin Jingbo

机构信息

Department of Polymer Materials, Shanghai University, 333 Nanchen Road, Shanghai 200444, China.

出版信息

J Mater Chem B. 2015 Feb 14;3(6):1020-1031. doi: 10.1039/c4tb01333f. Epub 2014 Dec 11.

DOI:10.1039/c4tb01333f
PMID:32261981
Abstract

In search of an injectable cellular delivery vehicle for tissue regeneration, porous microspheres fabricated from the synthetic polypeptide of poly(γ-benzyl-l-glutamate) (PBLG) were developed. The structural and morphological characteristics of the microspheres could be adjusted by changing the amounts of the gelatin porogen. PBLG microspheres fabricated from 6.5% gelatin content exhibited an average pore diameter of 50.9 ± 10.3 μm and a porosity of 86.58 ± 2.37%. Degradation in vitro of the microspheres could be well controlled by adjusting the molecular weight of PBLG, and the degradability in vivo showed a satisfactory degradation time range from 8 to 12 weeks. Articular chondrocytes, which were seeded within the PBLG porous microspheres, exhibited progressive proliferation and deposition of the cartilaginous extracellular matrix. After cultivation for 2 days in vitro, the PBLG porous microspheres loaded with chondrocytes were injected subcutaneously into nude mice. At 4, 8 and 12 weeks post-injection, neo-generated tissue was harvested for histological observations, which showed a typical cartilage structure and cartilaginous matrix accumulation. A gradual increase of GAG and COL II content in neo-generated tissue was detected by biochemical analysis. These results indicate that the fabricated porous microspheres showing controllable degradation properties, good biocompatibility and cytocompatibility are potentially useful as an injectable vehicle for cartilage tissue engineering.

摘要

为寻找用于组织再生的可注射细胞递送载体,开发了由聚(γ-苄基-L-谷氨酸)(PBLG)合成多肽制成的多孔微球。微球的结构和形态特征可通过改变明胶致孔剂的用量来调节。由6.5%明胶含量制成的PBLG微球平均孔径为50.9±10.3μm,孔隙率为86.58±2.37%。通过调节PBLG的分子量可以很好地控制微球的体外降解,体内降解性显示出8至12周的令人满意的降解时间范围。接种在PBLG多孔微球内的关节软骨细胞表现出软骨细胞外基质的逐渐增殖和沉积。在体外培养2天后,将负载软骨细胞的PBLG多孔微球皮下注射到裸鼠体内。在注射后4、8和12周,采集新生组织进行组织学观察,结果显示出典型的软骨结构和软骨基质积累。通过生化分析检测到新生组织中GAG和COL II含量逐渐增加。这些结果表明,所制备的多孔微球具有可控的降解性能、良好的生物相容性和细胞相容性,有望作为软骨组织工程的可注射载体。

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