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Title
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Corneal endothelial tissue engineering : from biological to synthetic scaffolds
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Author
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Abstract
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| The corneal endothelium is the most inner cell layer of the human cornea, which is the transparent window of the eye. It functions as a leaky barrier to facilitate to exchange of nutrients and water to the avascular cornea. It is a monolayer of hexagonal cells with the foremost task to maintain the cornea’s specific hydration status and thus concomitant transparency. However, they do not possess the proper machinery for tissue regeneration. That is why the absolute number of cells only decreases throughout life. When the process of inevitable cells loss is aggravated by disease or (surgical) trauma, the cornea will inadvertently swell and lose its transparency, which leads to visual impairment and blindness. If left untreated, this results in the formation of epithelial bullae, blisters on the front side of the cornea, which cause excruciating pain for the patient on top of visual impairment. At this moment, such patients can only be helped through the transplantation of a donor endothelium from a cadaveric cornea. Despite good clinical outcomes, the amount of available donor corneas does not meet the tissue demand. That is why I explored the cultivation of human corneal endothelial cells on different substrates to develop an ex vivo grown corneal endothelium. In this way, the global donor shortage could be alleviated by providing a therapy to multiple patients with one donor cornea. In this thesis, three different substrates were tested for their propensity to act as a cell scaffold for corneal endothelial culture and transplantation. The first two, the human anterior lens capsule and a collagen fish scale derived scaffold, were biologically derived, but were not appropriate for the proposed application. On the one side, the anterior lens capsule displayed good cytocompatibility, but had a rather limited diameter and was still dependent on a donor supply. On the other side, the fish scale scaffold displayed an extensive surface topography which hampered monolayer formation. That is why we have investigated a third scaffold, namely a synthetic ultrathin scaffold that was developed in collaboration with UGent, composed of a poly-(D,L)-lactic acid base and a gelatin coating. Initial experiments show optimal physicochemical properties and a biological proof-of-concept to grow immortalized and primary corneal endothelial cells. In the future, this novel composite scaffold will further be investigated in an ex vivo model of corneal endothelial transplantation before being tested in a rabbit model of corneal endothelial keratoplasty. |
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Language
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English
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Publication
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Antwerp
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University of Antwerp, Faculty of Medicine and Health Sciences, Department of Translational Neurosciences
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2020
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Volume/pages
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327 p.
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Note
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Koppen, Carina [Supervisor]
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Ní Dhubhghaill, Sorcha [Supervisor]
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Zakaria, Nadia [Supervisor]
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Full text (open access)
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