PTMAc-PEG-PTMAc hydrogel modified by RGDC and hyaluronic acid promotes neural stem cells' survival and differentiation in vitro
PTMAc-PEG-PTMAc hydrogel modified by RGDC and hyaluronic acid promotes neural stem cells' survival and differentiation in vitro
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RGDC和透明质酸修饰的PTMAc-PEG-PTMAc水凝胶促进神经干细胞体外存活和分化
DOI：
10.1039/c7ra06614g
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发表时间：
2017
期刊：
影响因子：
3.9
通讯作者：
Deng David Y B
中科院分区：
文献类型：
--
作者：
Yang Ruirui;Xu Caixia;Wang Tao;Wang Yuanqi;Wang Jingnan;Quan Daping;Deng David Y B
利用生物活性分子对水凝胶进行表面改性以提高其生物学性能，特别是在移植细胞治疗中枢神经系统损伤方面具有重要意义。本研究的目的是开发一种新型的聚乙二醇（PEG）基水凝胶修饰的Arg-Gly-Asp-Cys（RGDC）和透明质酸（HA）作为载体的神经干细胞（NSCs）的应用在中枢神经系统疾病。成功合成了这些新型凝胶，并通过GPC曲线和1H NMR进行了表征。随着HA含量的增加，凝胶的G′值增大，并用SEM对凝胶的孔径进行了表征。我们评估了体外不同比例的RGDC和HA修饰的水凝胶上的神经干细胞的粘附、存活和分化。粘附在30%RGDC水凝胶上的NSC的数量显著高于粘附在10%和20%RGDC水凝胶上的NSC的数量。然而，只有74%的NSC在30%RGDC水凝胶中存活。为了进一步提高NSC的存活率，将不同比例的HA添加到30%RGDC水凝胶中以产生凝胶-1（HA 33%）和凝胶-2（HA 50%）。我们发现，与30%RGDC水凝胶相比，两种凝胶制剂，特别是Gel-1，增加了NSC的存活率和分化率。此外，Gel-1在1、4和8周时对脊髓损伤大鼠的NSC、斑马鱼胚胎发生以及肝脏和肾脏表现出低毒性。我们的结论是，这种新的水凝胶（凝胶-1）具有良好的生物相容性，并能促进神经干细胞的存活和分化为神经元。它可以作为一个有前途的生物支架治疗中枢神经系统疾病的未来。
The enhancement of the biological properties of hydrogels by surface modifying with bioactive molecules is of great significance, especially for the treatment of central nervous system injury by combining engrafted cells. This study aimed to develop a novel polyethylene glycol (PEG)-based hydrogel modified by Arg-Gly-Asp-Cys (RGDC) and hyaluronic acid (HA) as a carrier of neural stem cells (NSCs) for applications in central nervous system disorders. These novel gels were synthesized successfully and confirmed by GPC curve and 1H NMR. The G′ increased with the increase in the contents of HA in the blends and the pore size of the hydrogels was detected by SEM. We evaluated the adhesion, survival, and differentiation of NSCs on hydrogels modified by different proportions of RGDC and HA in vitro. The number of NSCs adherent on a 30% RGDC hydrogel was significantly higher than the number of NSCs adherent on 10% and 20% RGDC hydrogels. However, only 74% of the NSCs were viable in the 30% RGDC hydrogel. To further improve the survival rate of the NSCs, different proportions of HA were added to the 30% RGDC hydrogel to create Gel-1 (HA 33%) and Gel-2 (HA 50%). We found that both gel formulations, particularly Gel-1, increased the survival and differentiation rates of NSCs compared to the 30% RGDC hydrogel. Furthermore, Gel-1 exhibited low toxicity to NSCs, zebrafish embryogenesis, as well as the liver and kidneys in rats with spinal cord injuries at 1, 4, and 8 weeks. We conclude that this novel hydrogel (Gel-1) has good biocompatibility and can promote NSCs survival and differentiation into neurons. It could be used as a promising biological scaffold to treat central nervous system disorders in the future.