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Title: High density collagen gels and their use in investigating corneal biology
Author: Foster, James William
Awarding Body: University of Reading
Current Institution: University of Reading
Date of Award: 2013
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The cornea is the transparent tissue at the front of the eye which provides two thirds of the refractive index to incident light and allows focussing on to the light sensitive retina. The main focus of this thesis is to utilise recently reported biomimetic scaffolds of compressed collagen gels to investigate their potential use in both bio-engineering applications and as a tool to understand the fundamental biology of the cornea. These recently described scaffolds are mechanically superior to collagen sponges and have found used in tissue engineering of the amniotic membrane, bladder, skin and the cornea. Arguably the biggest hurdle for engineering the human anterior corneal tissues is the current inability to extract large numbers of keratocytes. This is not due to scarcity of the cells but rather that the cells do not respond well to current tissue culture systems used for cell expansion. In this thesis we will investigate the use of compressed collagen gels in modelling the cornea and demonstrate the application of this technology to model the effects of increased collagen density/ stiffness on limbal epithelial stem cell differentiation. We implicate the Hippo pathway as a key regulator of stem cell differentiation and homeostasis and correlate this with expression patterns seen in situ. We also demonstrate a key role for glucose availability in controlling the phenotype of keratocytes expanded in vitro and use these findings in conjunction with compressed collagen gels, to produce models of the cornea which have improved optical properties than previously demonstrated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available