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负载二甲双胍的可注射丝素蛋白微球用于治疗脊髓损伤

Metformin loaded injectable silk fibroin microsphere for the treatment of spinal cord injury.

作者信息

Han Qi, Zheng Tiantian, Zhang Linhui, Wu Ningling, Liang Jiaqi, Wu Hong, Li Guicai

机构信息

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, Nantong, P.R. China.

Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, P.R. China.

出版信息

J Biomater Sci Polym Ed. 2022 Apr;33(6):747-768. doi: 10.1080/09205063.2021.2014113. Epub 2021 Dec 26.

Abstract

The repair of spinal cord injury is a great challenge in clinical. Improving the microenvironment of the injured site is the key strategy for accelerating axon regeneration and synaptic formation. Herein, a kind of silk fibroin microspheres functionalized by metformin through dopamine was developed using water-in-oil emulsification-diffusion method and surface modification technique, and the effect on cortical neuron was evaluated. The results showed that the microspheres showed a uniform size distribution with the diameter of around 60 μm and a concave structure. Moreover, the microspheres possessed good injectability and stability. In addition, the metformin could be successfully immobilized in the silk fibroin microspheres. The cell culture results displayed that the growth and morphology of cortical neurons on the microspheres with metformin concentration of 5 mg/mL and 10 mg/mL were obviously better than that on other samples. Notably, the spread area of single cortical cell on silk fibroin microspheres was increased with the ascending metformin concentration. Therefore, the results indicated that the metformin loaded silk fibroin microsphere could obviously improve the growth and spreading behavior of cortical neuron. The study may provide an important experimental basis for the development of drug loaded injectable biomaterials scaffolds for the treatment of spinal cord injury and have great potential for spinal cord regeneration.

摘要

脊髓损伤的修复在临床上是一项巨大的挑战。改善损伤部位的微环境是加速轴突再生和突触形成的关键策略。在此,采用油包水乳化扩散法和表面改性技术制备了一种通过多巴胺功能化的二甲双胍丝素蛋白微球,并评估了其对皮质神经元的影响。结果表明,微球尺寸分布均匀,直径约为60μm,呈凹形结构。此外,微球具有良好的可注射性和稳定性。另外,二甲双胍能够成功固定在丝素蛋白微球中。细胞培养结果显示,二甲双胍浓度为5mg/mL和10mg/mL的微球上皮质神经元的生长和形态明显优于其他样品。值得注意的是,随着二甲双胍浓度的升高,单个皮质细胞在丝素蛋白微球上的铺展面积增加。因此,结果表明负载二甲双胍的丝素蛋白微球能够明显改善皮质神经元的生长和铺展行为。该研究可能为开发用于治疗脊髓损伤的载药可注射生物材料支架提供重要的实验依据,并且在脊髓再生方面具有巨大潜力。

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