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Title: Elucidation of porcine corneal ultrastructure to inform development of corneal xenographs or biomimetic replacements
Author: Howkins, Ashley
ISNI:       0000 0004 5368 6034
Awarding Body: University of Brighton
Current Institution: University of Brighton
Date of Award: 2015
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The transparent, anterior-most tissue of the eye globe, which allows light into the eye for sight, is the cornea. The main thickness of the cornea, known as the stroma, is a collagenous extra cellular matrix (ECM) that is comprised of fibrous collagen types I, V and VI along with keratan sulphate (KS) and chondroitin/dermatan sulphate (CS/DS) proteoglycans. These components maintain the collagen fibrils in a quasi-crystalline arrangement, which enables the tissue to be transparent. Diseases or injuries to the cornea disrupt the ECM architecture resulting in visual impairment due to a loss of transparency with treatment often requiring transplantation of a corneal allograft. However, corneal allografts can fail and transmission of undetectable infective agents is also a potential risk. Decellularised porcine corneal tissue and in-vitro produced stromal ECM replacements have shown great potential to generate tailor-made artificial corneal replacements. However, as yet no microscopic analysis of the porcine stromal ECM has been made and also in-vitro produced corneal biomaterials are often created solely using collagen type I. This investigation used transmission electron microscopy to elucidate upon the full-depth three-dimensional architecture of the porcine stromal ECM; which provided a better understanding of the ECM architecture along with the mechanisms of transparency and the comparability of porcine stromal tissue to human stromal tissue. Moreover, decellularised and swollen porcine corneal stromal tissue was used as a scaffold to re-infiltrate primary human corneal keratocytes into the tissue to generate a humanised porcine corneal xenograft; with transparency being restored by dehydrating the tissue in dextran. Additionally, a novel biomimetic collagen types I and V and CS/DS hydrogel was created and possessed improved light transmission over a collagen type I only hydrogel as well as being able to host primary human corneal stromal cells. It was concluded, that the corneal ECM architecture plays an important role in corneal transparency and future work into corneal replacements should consider utilising cues from the corneal stromal ECM architecture and components to generate enhanced artificial corneal stromal replacements.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: A000 Medicine