Development of a Novel 3D Culture System for ScreeningFeatures of a Complex Implantable Device for CNS Repair

摘要

Tubular scaffolds which incorporate a variety of micro- and nanotopographies have a wide application potential in tissue engineering especially for the repair of spinal cord injury (SCI). We aim to produce metabolically active differentiated tissues within such tubes, as it is crucially important to evaluate the biological performance of the three-dimensional (3D) scaffold and optimize the bioprocesses for tissue culture. Because of the complex 3D configuration and the presence of various topographies, it is rarely possible to observe and analyze cells within such scaffolds in situ. Thus, we aim to develop scaled down mini-chambers as simplified in vitro simulation systems, to bridge the gap between two-dimensional (2D) cell cultures on structured substrates and three-dimensional (3D) tissue culture. The mini-chambers were manipulated to systematically simulate and evaluate the influences of gravity, topography, fluid flow, and scaffold dimension on three exemplary cell models that play a role in CNS repair (i.e., cortical astrocytes, fibroblasts, and myelinating cultures) within a tubular scaffold created by rolling up a microstructured membrane. Since weuse CNS myelinating cultures, we can confirm that the scaffold doesnot affect neural cell differentiation. It was found that heterogeneouscell distribution within the tubular constructs was caused by a combinationof gravity, fluid flow, topography, and scaffold configuration, whilecell survival was influenced by scaffold length, porosity, and thickness.This research demonstrates that the mini-chambers represent a viable,novel, scale down approach for the evaluation of complex 3D scaffoldsas well as providing a microbioprocessing strategy for tissue engineeringand the potential repair of SCI.