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The Effect of Mechanical Stimulation on Osteogenesis of Cell Seeded Collagen Microspheres

Shariatzadeh, Maryam (2016) The Effect of Mechanical Stimulation on Osteogenesis of Cell Seeded Collagen Microspheres. PhD thesis, University of Sheffield.

Text (PhD thesis)
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Mesenchymal stem cells (MSCs) are widely implicated as a cell source for tissue engineering of skeletal tissue in cell based therapy. Mechanical forces can stimulate the differentiation of MSCs in microenvironment and the resulting mechanotransduction would provide crucial adjuncts to customary biochemical signalling pathways. This study indicated that collagen concentration, hence cells micro environment mechanical properties are important in cell proliferation and differentiation process. The experimental results showed that collagen concen- tration of 2mg/mL supports proliferation of MSCs while, higher concentrations promote the viability of more differentiated cell lines human osteosarcoma (MG- 63s).Encapsulated human embryonic stem cell-derived mesenchymal progenitor (hES-MPs) contraction is vital in cell adaptation and remodeling of their new envi- ronment. hES-MPs seeded collagen microspheres were subjected to two cyclic compression regimes and cell viability, alkaline phosphatase (ALP) activity and mineralisation of differentiated cells were assessed over 28 days experiment. It has been shown that cyclic compression of very low cell number seeded on soft natural scaffold can encourage osteogenesis of undifferentiated cells. Applying mechanical stimulation can affect cell commitment but at the same time it shows that mechanical loading and in particular fluid-induced shear stress (FSSs) on their own fail to provide all the necessary signals in osteogenic differentiation of hES-MPs. Combining microfluidic systems with mechanical stimulation for osteogenesis represents a scientific and technological innovation. This study demonstrated a microfluidic chamber design for mechanical stimulation of flexible cellular microspheres and a possible high-throughput microfluidic system for parallel processing of stem cell aggregation. Microfluidic system can increase the ALP activity of cells while maintaining cell viability and proliferation. Self-assembled hES-MPs collagen microspheres present exceptional cell delivery model in bone healing and repair process and in addressing many inadequacies of the existing cell delivery approaches. Cell seeded collagen microspheres offer great possibilities in facilitating the clinical application of cell-based therapy in local bone remodelling and regenerative medicine.

Item Type: Thesis (PhD)
Academic Units: The University of Sheffield > Faculty of Engineering (Sheffield) > Mechanical Engineering (Sheffield)
Identification Number/EthosID: uk.bl.ethos.686508
Depositing User: Mrs Maryam Shariatzadeh
Date Deposited: 26 May 2016 14:30
Last Modified: 03 Oct 2016 13:12
URI: http://etheses.whiterose.ac.uk/id/eprint/13031

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