Esmaeili, Maryam (2018). Development and characterisation of systems for the delivery of an antiscarring molecule (decorin) for use after corneal injury and cutaneous burn. University of Birmingham. Ph.D.
Full text not available from this repository.Abstract
Introduction: Transforming growth factor-β1 (TGF-β1) is a key cytokine that promotes fibrosis after injury in many adult tissues. Here, we hypothesise that delivery of human recombinant decorin (hr-decorin), a natural antagonist of TGF-β1, loaded into gellan-based biomembrane sheet dressings and fluid gel eye drops, prevents cutaneous and corneal scarring after injury.
Methods: Gellan-based wound dressings loaded with hr-decorin were characterised for swelling, release profile of hr-decorin, systemic absorption of hr-decorin and human skin reactions. Topical gellan-based fluid gels loaded with hr-decorin were also tested for penetration of hr-decorin into the cornea and aqueous humour (AqH). The effect of hr-decorin on cell migration, differentiation and expression of scar-associated molecules of TGF-β1-stimulated human dermal fibroblasts (HDF) was also evaluated.
Results: Gellan-based wound dressings had a high fluid uptake capacity, no adverse reactions on human skin, and sustained local release but no systemic absorption of hr-decorin after application to pig mid-dermal burns. Gellan-based fluid gel eye drops also released hr-decorin over time, which penetrated the cornea and was detected in AqH. The mRNA expression of scar-associated molecules in cultured TGF-β1-stimulated HDF was significantly decreased by hr-decorin, but no changes at the protein level were detected.
Conclusion: The results suggest that delivery of Decorin through gellan-based wound dressing and fluid gel eye drop formulations have the potential for translation into therapies for cutaneous and corneal scarring.
| Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||
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| Award Type: | Doctorates > Ph.D. | |||||||||
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| College/Faculty: | Colleges (2008 onwards) > College of Medical & Dental Sciences | |||||||||
| School or Department: | Institute of Inflammation and Ageing | |||||||||
| Funders: | Wellcome Trust | |||||||||
| Subjects: | Q Science > QH Natural history > QH301 Biology R Medicine > RE Ophthalmology |
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| URI: | http://etheses.bham.ac.uk/id/eprint/8387 |
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