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.

Chemotaxis and cell migration are important processes for life, involved in organism development and homeostasis and implicated in a number of disease states. Dictyostelium discoideum, an amoeba, is a useful model for investigation of chemotaxis and development, due to its ability to undergo chemotactic aggregation and development upon starvation. Although cell migration has been well described on planar transparent surfaces, it is uncertain how well these conditions replicate the natural environment of a cell. However, attempts to better replicate these environments generally make use of opaque substrates and 3D matrices, in which it is more challenging to image cell migration. Protocols were developed to enable optical coherence tomography, a 3D structural imaging technique which requires no sample processing or staining, to be successfully employed in imaging Dictyostelium cell migration in time-lapse on non-transparent substrata and within an agarose gel. I compared the effects of two substrates, a nitrocellulose filter and a polystyrene Petri dish on aggregating cells and found differences in speed but not persistence. Extension of this to include cells within agarose revealed that these cells exhibited less directed migration, but their velocity was unaffected. I showed that cells lacking myosin II failed to complete development within an agarose gel and had significantly reduced velocity and directional migration when compared to their parent strain. Furthermore, the velocities of cells migrating within agarose gel were bimodally distributed, potentially indicating two distinct cell populations, fast and slow, and fast movement was shown to be largely myosin II dependent. Great potential therefore exists for cell-substrate and cell-matrix interactions to affect the migration character of cells, even those, such as Dictyostelium, which do not form strong focal adhesions. Moreover a properly ordered cytoskeleton is implicated in enabling cells to effectively utilise different modes of cell motility.