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Title: Polymeric amniotic membrane substitute for ocular surface reconstruction and drug delivery
Author: Tint, Naing Latt
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2013
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Introduction Corneal blindness is a major cause of blindness and may result from infection, inflammation and trauma leading to melting, scarring and perforation with potential loss of sight or eye. The amniotic membrane (AM) has been utilised in ophthalmology as a bandage, graft or a means of cell carrier for transplantation. The biochemical constituents of amniotic membrane have been shown to exhibit intra and inter donor variability. Aim To fabricate a polymer scaffold substitute for the AM that may be combined with a hydrogel containing pooled extracts from multiple AM, that may be utilised for ocular surface reconstruction and drug delivery. Methods Poly Lactic-co-Glycolic Acid (PLGA) micro and nanofibrous scaffolds were fabricated using electrospinning. A thermoreversible (Poly Lactic-co-Glycolic Acid-Polyethylene Glycol-Poly Lactic-co-Glycoiic Acid) hydrogel was synthesised by ring opening polymerisation and was characterised by Nuclear Magnetic Resonance (NMR), Gel Permeation Chromatography (GPC) and rheology. Cytotoxicity testing was undertaken using corneal stromal cells and cell characterisation undertaken using qPCR and immunofluorescence. The cellular response to pooled extracts of AM was assessed. Ciprofloxacin release profiles from the hydrogel and the antimicrobial activity against Pseudomonas aeruginosa and Escherichia coli were determined. Results Microfibrous scaffolds and PLGA-PEG-PLGA hydrogel were both shown to be cytocompatible. Cornea stromal cells were able to penetrate the microfibrous scaffolds and were shown to revert to a more quiescent phenotype similar to the AM stroma. In contrast to AM the polymer scaffold displayed a greater ability to resist the influence of collagenases. The pooled extract of AM displayed deleterious effects on corneal stromal cells and was excluded from use in further experiments. Ciprofloxacin was demonstrated to have sustained and controlled release from the PLGA-PEG-PLGA hydrogel. The released drug displayed sufficient antimicrobial activity with more prolonged release from the higher concentration hydrogels. Conclusion This is the first report of the potential use of electrospun scaffold and hydrogel for corneal stromal regeneration and drug delivery. The combined scaffold and hydrogel may have potential as a standardised polymeric substitute for the AM that is easy and cheap to manufacture and is available "off the shelf".
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available