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Title: Engineering 3D Cellular Constructs Using Inter - Cellular Polymeric Linker
Keywords: cell aggregates, PEI-hydrazide, 3-dimensional in vitro, microfluidics, spheroid, tissue engineering
Issue Date: 30-Dec-2008
Citation: ONG SIEW MIN (2008-12-30). Engineering 3D Cellular Constructs Using Inter - Cellular Polymeric Linker. ScholarBank@NUS Repository.
Abstract: Three-dimensional cell cultures are indispensible as they mimic the cell-cell and cell-matrix interactions in vivo. To date, biomaterials like scaffolds and hydrogels have been used for engineering 3D cellular or tissue constructs. However, the introduction of such bulk biomaterials might not be suitable for engineering constructs of cell-dense and matrix-poor tissues of the internal organs. To engineer 3D cellular and tissue constructs with minimal biomaterials, we developed an inter-cellular polymeric linker to facilitate cell-cell interaction and cellular aggregation. The cells in the cellular aggregates proliferated, grew compact and maintained 3D cell morphology while the inter-cellular linker disappeared from the cell surfaces in 5 days. Structural characterisation and functional assessment showed that the cellular aggregates remodeled during culture to exhibit features of a mature 3D spheroid with formation of adherens junctions, secretion of extra-cellular matrix, development of gradients of cell proliferation and oxygen concentration from the periphery to the centre, good cellular functions and resistance to drug penetration. We further incorporated the use of the inter-cellular linker into a 3D microfluidics system to take advantage of the micron-scale and fluidic properties for applications, and at the same time we created a novel method for seeding and culturing mammalian cells three-dimensionally in microfluidic systems without hydrogels. The 3D microfluidic cellular constructs exhibited higher cellular functions than 2D-cultured cells and demonstrated potential for real-time optical-based monitoring of cellular events with good spatial and temporal resolution. The inter-cellular linker hence allows the formation of functional 3D cell-dense constructs for tissue engineering applications.
Appears in Collections:Ph.D Theses (Open)

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