Tissue engineering in hostile environments: The effects and control of inflammation in bone tissue engineering
PhD Supervisor(s): Lee Buttery
Contact Email:laura.sidney@nottingham.ac.uk
Undergraduate Degree: MEng Biomaterial Science and Tissue Engineering (University of Sheffield)
PhD Summary
My research focused on the effect and potential control of inflammation in bone tissue engineering, particularly directed toward the use of osteogenically differentiated embryonic stem cells (osteo-ESCs). This work involved a comparison of in vitro osteogenic differentiation between the osteo-ESCs and extracted primary osteoblasts, in addition to the development of an in vitro simulation of an inflammatory environment using interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). The in vitro inflammation model was subsequently used to assess differences in biochemical responses and effect on osteogenic differentiation of osteo-ESCs and primary osteoblasts.
Although the osteo-ESCs showed expression of osteogenic markers, closer analysis revealed that differentiation differed extensively to that of primary osteoblasts, and there was a large amount of cell heterogeneity within the ESC population. Results from the inflammation model also revealed marked differences between the responses of the primary osteoblasts and the osteo-ESCs. The conclusion of this work was that although osteogenic differentiation strategies for ESCs are well-established in literature, there have been few comparative studies and further optimisation is required. To follow on from this work, a cell sorting-strategy was developed to refine the osteo-ESC population and subsequent analysis of the sorted cell population revealed a phenotype and response to proinflammatory cytokines that was far more similar to the primary osteoblasts.
An alternative focus of my PhD concentrated on uses of bone tissue engineering strategies to control and modulate levels of inflammation. I utilised the temperature-sensitive PLGA/PEG particles scaffolds, developed at Nottingham University and adapted them to release anti-inflammatory drugs. The release of drugs was then tested using an in vitro inflammatory model using the primary osteoblasts.
Skills & Techniques
Publications, Presentations and Awards
Publications
M.J. Sawkins, W. Bowen, P. Dhadda, H. Markides, LE Sidney, A.J. Taylor, F.R.A.J. Rose, S.F. Badylak, K.M. Shakesheff & L.J. White. 2013, Hydrogels Derived from Demineralized and Decellularized Bone Extracellular Matrix, Acta Biomaterialia, 9(8), 7865-73
Oral Presentations
Poster Presentations
Current Employment:
Postdoctoral research fellow in the Division of Ophthalmology, University of Nottingham, working on the role of CD34 in mesenchymal to epithelial transdifferentiation of corneal stromal stem cells.
