A tenascin-C mimetic peptide amphiphile nanofiber gel promotes neurite outgrowth and cell migration of neurosphere-derived cells.

A tenascin-C mimetic peptide amphiphile nanofiber gel promotes neurite outgrowth and cell migration of neurosphere-derived cells.
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DOI:
10.1016/j.actbio.2016.04.010
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发表时间:
2016-06
期刊:
影响因子:
9.7
通讯作者:
Stupp SI
Stupp SI
中科院分区:
工程技术1区
文献类型:
--
作者:
Berns EJ;Álvarez Z;Goldberger JE;Boekhoven J;Kessler JA;Kuhn HG;Stupp SI

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仿生材料显示来自细胞外基质分子如层粘连蛋白和纤连蛋白的天然生物活性信号,有望促进神经系统的再生。在这项工作中,我们研究了一种仿生肽两亲物(PA),其呈现来自细胞外糖蛋白腱生蛋白-C的肽,已知其通过与β1整合素相互作用促进神经突生长。腱生蛋白-C模拟物PA(TN-C PA)被发现自组装成超分子纳米纤维,并且通过共组装被并入由高度排列的纳米纤维形成的PA凝胶中。这些凝胶中TN-C PA含量增加了从包裹的P19细胞分化的神经元产生的神经突的长度和数量。此外,发现含有TN-C PA的凝胶增加了细胞从在凝胶涂层上培养的神经球中迁移出来。这些生物活性凝胶可以作为人工基质疗法在区域的神经元损失,以引导神经干细胞,并通过生化线索促进分化后的神经突延伸。重要靶点的一个例子是它们在脊髓损伤中作为生物材料治疗的用途。
Biomimetic materials that display natural bioactive signals derived from extracellular matrix molecules like laminin and fibronectin hold promise for promoting regeneration of the nervous system. In this work, we investigated a biomimetic peptide amphiphile (PA) presenting a peptide derived from the extracellular glycoprotein tenascin-C, known to promote neurite outgrowth through interaction with β1 integrin. The tenascin-C mimetic PA (TN-C PA) was found to self-assemble into supramolecular nanofibers and was incorporated through co-assembly into PA gels formed by highly aligned nanofibers. TN-C PA content in these gels increased the length and number of neurites produced from neurons differentiated from encapsulated P19 cells. Furthermore, gels containing TN-C PA were found to increase migration of cells out of neurospheres cultured on gel coatings. These bioactive gels could serve as artificial matrix therapies in regions of neuronal loss to guide neural stem cells and promote through biochemical cues neurite extension after differentiation. One example of an important target would be their use as biomaterial therapies in spinal cord injury.