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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:753117 |
| Date | January 2018 |
| Creators | Esmaeili, Maryam |
| Publisher | University of Birmingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.bham.ac.uk//id/eprint/8387/ |
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