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• W2783202420 abstract "Neurotrauma and neurodegenerative disease often result in lasting neurological deficits due to the limited capacity of the central nervous system (CNS) to replace lost neurons and regenerate axonal pathways. However, during nervous system development, neuronal migration and axonal extension often occur along pathways formed by other cells, referred to as living scaffolds. Seeking to emulate these mechanisms and to design a strategy that circumvents the inhibitory environment of the CNS, this manuscript presents a protocol to fabricate tissue engineered astrocyte-based living scaffolds. To create these constructs, we employed a novel biomaterial encasement scheme to induce astrocytes to self-assemble into dense three-dimensional bundles of bipolar longitudinally-aligned somata and processes. First, hollow hydrogel micro-columns were assembled, and the inner lumen was coated with collagen extracellular-matrix. Dissociated cerebral cortical astrocytes were then delivered into the lumen of the cylindrical micro-column and, at a critical inner diameter of <350 µm, spontaneously self-aligned and contracted to produce long fiber-like cables consisting of dense bundles of astrocyte processes and collagen fibrils measuring <150 µm in diameter yet extending several cm in length. These engineered living scaffolds exhibited >97% cell viability and were virtually exclusively comprised of astrocytes expressing a combination of the intermediate filament proteins glial-fibrillary acidic protein (GFAP), vimentin, and nestin. These aligned astrocyte networks were found to provide a permissive substrate for neuronal attachment and aligned neurite extension. Moreover, these constructs maintain integrity and alignment when extracted from the hydrogel encasement, making them suitable for CNS implantation. These preformed constructs structurally emulate key cytoarchitectural elements of naturally occurring glial-based living scaffolds in vivo. As such, these engineered living scaffolds may serve as test-beds to study neurodevelopmental mechanisms in vitro or facilitate neuroregeneration by directing neuronal migration and/or axonal pathfinding following CNS degeneration in vivo." @default.
• W2783202420 created "2018-01-26" @default.
• W2783202420 creator A5012617349 @default.
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• W2783202420 date "2018-01-10" @default.
• W2783202420 modified "2023-10-17" @default.
• W2783202420 title "Three-dimensional Tissue Engineered Aligned Astrocyte Networks to Recapitulate Developmental Mechanisms and Facilitate Nervous System Regeneration" @default.
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• W2783202420 doi "https://doi.org/10.3791/55848" @default.
• W2783202420 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5908484" @default.
• W2783202420 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29364269" @default.
• W2783202420 hasPublicationYear "2018" @default.
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