Bruder Jan M, Lee Andrea P, Hoffman-Kim Diane
Center for Biomedical Engineering and Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI 02912, USA.
J Biomater Sci Polym Ed. 2007;18(8):967-82. doi: 10.1163/156856207781494412.
It is well established that Schwann cells (SCs) promote and enhance axon guidance and nerve regeneration by providing multiple cues, including extracellular matrix, cell surface molecules, neurotrophic factors and cellular topography. Which of the elements of the complex environment associated with SCs provides the essential information for directed nerve growth is unclear, because, until now, it has been impossible to investigate their contributions individually. Our development of biomimetic materials that replicate the micro- and nanoscale topography of SCs has allowed us to investigate for the first time the role of cellular topography in directing nerve growth. Dorsal root ganglion (DRG) neurons were cultured on flat poly(dimethyl siloxane) (PDMS) and on PDMS replicas with protruding SC topography. Image analysis showed that more neurons adhered to the replicas than to the flat substrates, and that neurite growth on the replicas followed the underlying SC pattern. Neuronal alignment was dependent on cell density. Live SCs derived from the DRG also grew along the replica SC pattern. These results suggest that the combination of micro- and nanoscale topographical cues provided by SCs can influence nerve growth and point toward design parameters for future nerve guidance channels.
众所周知,施万细胞(SCs)通过提供多种信号促进和增强轴突导向及神经再生,这些信号包括细胞外基质、细胞表面分子、神经营养因子和细胞拓扑结构。与施万细胞相关的复杂环境中的哪些要素为定向神经生长提供了关键信息尚不清楚,因为直到现在,还无法单独研究它们的作用。我们开发的仿生材料能够复制施万细胞的微米和纳米级拓扑结构,这使我们首次能够研究细胞拓扑结构在引导神经生长中的作用。将背根神经节(DRG)神经元培养在平坦的聚二甲基硅氧烷(PDMS)上以及具有突出施万细胞拓扑结构的PDMS复制品上。图像分析表明,与平坦底物相比,更多的神经元附着在复制品上,并且复制品上的神经突生长遵循潜在的施万细胞模式。神经元排列取决于细胞密度。源自背根神经节的活施万细胞也沿着复制品施万细胞模式生长。这些结果表明,施万细胞提供的微米和纳米级拓扑信号的组合可以影响神经生长,并为未来神经导向通道的设计参数指明了方向。