Berns Eric J, Álvarez Zaida, Goldberger Joshua E, Boekhoven Job, Kessler John A, Kuhn H Georg, Stupp Samuel I
Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, USA.
Acta Biomater. 2016 Jun;37:50-8. doi: 10.1016/j.actbio.2016.04.010. Epub 2016 Apr 7.
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.
Tenascin-C is an important extracellular matrix molecule in the nervous system and has been shown to play a role in regenerating the spinal cord after injury and guiding neural progenitor cells during brain development, however, minimal research has been reported exploring the use of biomimetic biomaterials of tenascin-C. In this work, we describe a selfassembling biomaterial system in which peptide amphiphiles present a peptide derived from tenascin-C that promotes neurite outgrowth. Encapsulation of neurons in hydrogels of aligned nanofibers formed by tenascin-C-mimetic peptide amphiphiles resulted in enhanced neurite outgrowth. Additionally, these peptide amphiphiles promoted migration of neural progenitor cells cultured on nanofiber coatings. Tenascin-C biomimetic biomaterials such as the one described here have significant potential in neuroregenerative medicine.
呈现源自细胞外基质分子（如层粘连蛋白和纤连蛋白）的天然生物活性信号的仿生材料有望促进神经系统的再生。在这项研究中，我们研究了一种仿生肽两亲分子（PA），它呈现一种源自细胞外糖蛋白腱生蛋白-C的肽，已知该肽通过与β1整合素相互作用促进神经突生长。发现腱生蛋白-C模拟PA（TN-C PA）能自组装成超分子纳米纤维，并通过共组装掺入由高度排列的纳米纤维形成的PA凝胶中。这些凝胶中的TN-C PA含量增加了从包封的P19细胞分化而来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的凝胶能增加细胞从凝胶涂层上培养的神经球中迁出的迁移率。这些生物活性凝胶可作为神经元缺失区域的人工基质疗法，以引导神经干细胞，并在分化后通过生化信号促进神经突延伸。一个重要的应用靶点示例是将它们用作脊髓损伤的生物材料疗法。
腱生蛋白-C是神经系统中一种重要的细胞外基质分子，已被证明在损伤后脊髓再生以及脑发育过程中引导神经祖细胞方面发挥作用，然而，关于探索腱生蛋白-C仿生生物材料应用的研究报道极少。在这项研究中，我们描述了一种自组装生物材料系统，其中肽两亲分子呈现一种源自腱生蛋白-C的肽，该肽可促进神经突生长。将神经元封装在由腱生蛋白-C模拟肽两亲分子形成的排列纳米纤维水凝胶中可增强神经突生长。此外，这些肽两亲分子促进了在纳米纤维涂层上培养的神经祖细胞的迁移。本文所述的腱生蛋白-C仿生生物材料在神经再生医学中具有巨大潜力。
