University of Michigan, 1150 W. Medical Center Drive, 5323A Med Sci I, Ann Arbor, MI 48109, USA.
Biomacromolecules. 2012 Nov 12;13(11):3427-38. doi: 10.1021/bm301220k. Epub 2012 Oct 26.
There is little remedy for the devastating effects resulting from neuronal loss caused by neural injury or neurodegenerative disease. Reconstruction of damaged neural circuitry with stem cell-derived neurons is a promising approach to repair these defects, but controlling differentiation and guiding synaptic integration with existing neurons remain significant unmet challenges. Biomaterial surfaces can present nanoscale topographical cues that influence neuronal differentiation and process outgrowth. By combining these scaffolds with additional molecular biology strategies, synergistic control over cell fate can be achieved. Here, we review recent progress in promoting neuronal fate using techniques at the interface of biomaterial science and genetic engineering. New data demonstrates that combining nanofiber topography with an induced genetic program enhances neuritogenesis in a synergistic fashion. We propose combining patterned biomaterial surface cues with prescribed genetic programs to achieve neuronal cell fates with the desired sublineage specification, neurochemical profile, targeted integration, and electrophysiological properties.
对于由神经损伤或神经退行性疾病引起的神经元丢失所导致的破坏性影响，几乎没有补救措施。用干细胞衍生的神经元重建受损的神经回路是修复这些缺陷的一种很有前途的方法，但控制分化并引导与现有神经元的突触整合仍然是重大的未满足的挑战。生物材料表面可以呈现纳米级形貌线索，影响神经元的分化和突起的生长。通过将这些支架与其他分子生物学策略相结合，可以实现对细胞命运的协同控制。在这里，我们综述了生物材料科学和遗传工程界面技术促进神经元命运的最新进展。新的数据表明，将纳米纤维形貌与诱导的遗传程序相结合，以协同的方式增强神经突生成。我们建议将图案化生物材料表面线索与规定的遗传程序相结合，以实现具有所需亚系特异性、神经化学特征、靶向整合和电生理特性的神经元细胞命运。
