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仿生聚(丝氨酸六亚甲基脲)促进神经突生长和导向。

Biomimetic poly(serinol hexamethylene urea) for promotion of neurite outgrowth and guidance.

机构信息

a College of Engineering and Applied Science , University of Colorado Denver | Anschutz Medical Campus , 12700 E. 19th Avenue, Research 2 - Building P15, Aurora , CO 80045-2560 , USA.

出版信息

J Biomater Sci Polym Ed. 2014;25(4):354-69. doi: 10.1080/09205063.2013.861170. Epub 2013 Nov 27.

DOI:10.1080/09205063.2013.861170
PMID:24279744
Abstract

Nerve function recovery is a major technical challenge in the rehabilitation of patients suffering from severe neuropathies. Facilitating functional recovery requires the creation of a growth-permissive environment that directs the extension and myelination of surviving neurons. To this end, an electrospun nanofiber scaffold composed of arginine-glycine-aspartate-modified poly(serinol hexamethylene urea)-blend-poly-ε-caprolactone (PSHU-RGD/PCL) has been employed. Initially, we investigated the cytotoxicity of PSHU in PC12 cell culture. This was followed by functional examinations of PSHU-RGD for cell viability, proliferation, differentiation, and neurite outgrowth, and finally we examined electrospun scaffolds for guided neurite sprouting. MTT proliferation assays indicated no cytotoxic effects of polymer as compared to laminin-coated surfaces. Functional testing revealed PSHU-RGD surfaces to be comparable to the positive control, laminin-coated surface, in neurite outgrowth studies with average neurite lengths of 84.6 μm (laminin), 218.2 μm (PSHU-RGD), 570.2 μm (laminin + NGF), and 958.2 μm (PSHU-RGD + NGF) after two weeks on homogeneously modified surfaces, and 554.8 μm (nonwoven mats) and 1512.3 μm (uniaxially aligned mats) for PSHU-RGD/PCL + NGF scaffolds after one week. We created PSHU functionalized with the tripeptide, RGD, which provided chemical and physical cues to PC12 cell proliferation and differentiation. We expect that PSHU-RGD will be capable of directing and promoting neurite outgrowth in many neuropathy models.

摘要

神经功能恢复是严重神经病变患者康复的主要技术挑战。促进功能恢复需要创建一个有利于生长的环境,以指导存活神经元的延伸和髓鞘形成。为此,我们采用了一种由精氨酸-甘氨酸-天冬氨酸修饰的聚(丝氨酸六亚甲基脲)-共-聚-ε-己内酯(PSHU-RGD/PCL)组成的电纺纳米纤维支架。首先,我们研究了 PSHU 在 PC12 细胞培养中的细胞毒性。随后,我们对 PSHU-RGD 的细胞活力、增殖、分化和神经突生长进行了功能检测,最后我们研究了电纺支架对导向神经突发芽的作用。MTT 增殖测定表明,与层粘连蛋白涂层表面相比,聚合物没有细胞毒性。功能测试显示,在神经突生长研究中,PSHU-RGD 表面与阳性对照(层粘连蛋白涂层表面)相当,平均神经突长度分别为 84.6 μm(层粘连蛋白)、218.2 μm(PSHU-RGD)、570.2 μm(层粘连蛋白+NGF)和 958.2 μm(PSHU-RGD+NGF)在均匀修饰表面上培养两周后,以及 PSHU-RGD/PCL+NGF 支架培养一周后,无纺垫上为 554.8 μm,单轴取向垫上为 1512.3 μm。我们创建了精氨酸-甘氨酸-天冬氨酸三肽(RGD)功能化的 PSHU,它为 PC12 细胞增殖和分化提供了化学和物理线索。我们期望 PSHU-RGD 能够在许多神经病变模型中指导和促进神经突生长。

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