Morelli Sabrina, Piscioneri Antonella, Salerno Simona, Chen Chien-Chung, Chew Chee Ho, Giorno Lidietta, Drioli Enrico, De Bartolo Loredana
Institute on Membrane Technology, National Research Council of Italy, ITM-CNR, c/o University of Calabria, via P. Bucci cubo 17/C, I-87030 Rende (CS), Italy.
Biofabrication. 2017 May 17;9(2):025018. doi: 10.1088/1758-5090/aa6f6f.
An important challenge in neuronal tissue engineering is to create innovative tools capable of promoting cellular response in terms of neuronal differentiation and neurite orientation that may be used as investigational platforms for studying neurobiological events and neurodegenerative disorders. A novel membrane bioreactor was created to provide a 3D well-controlled microenvironment for neuronal outgrowth. The bioreactor consisted of poly-L-lactic acid highly aligned microtube array (PLLA-MTA) membranes assembled in parallel within a chamber that establish an intraluminal and an extraluminal compartment whose communication occurs through the pores of the MTA membrane walls. The bioreactor configuration provided a wide surface area for cell adhesion in a small volume, and offered a peculiar arrangement that directed neuronal orientation. The combination of an appropriate membrane porosity, pore interconnectivity and very thin walls ensured optimal indirect perfusion to cell compartment, and enhanced the mass transfer of metabolites and catabolites protecting neurons from shear stress. The PLLA-MTA membrane bioreactor promoted the growth and differentiation of SH-SY5Y cells toward a neuronal phenotype, and guided neurite alignment giving rise to a 3D neuronal tissue-like construct. It provides an innovative platform to study neurobiological phenomena in vitro and by guiding neuronal orientation for repair and/or regeneration.
神经组织工程中的一个重要挑战是创建创新工具，这些工具能够促进神经元分化和神经突定向方面的细胞反应，可用作研究神经生物学事件和神经退行性疾病的研究平台。创建了一种新型膜生物反应器，为神经元生长提供三维可控微环境。该生物反应器由聚-L-乳酸高度排列的微管阵列（PLLA-MTA）膜组成，这些膜在一个腔内平行组装，形成一个管腔和一个管腔外隔室，它们通过MTA膜壁的孔进行连通。该生物反应器配置在小体积内提供了用于细胞粘附的大表面积，并提供了一种引导神经元定向的特殊排列。适当的膜孔隙率、孔互连性和非常薄的壁的组合确保了对细胞隔室的最佳间接灌注，并增强了代谢产物和分解代谢产物的传质，保护神经元免受剪切应力。PLLA-MTA膜生物反应器促进了SH-SY5Y细胞向神经元表型的生长和分化，并引导神经突排列，形成三维神经元组织样构建体。它提供了一个创新平台，用于体外研究神经生物学现象，并通过引导神经元定向进行修复和/或再生。
