Modulation of Human Lens Epithelial Cell Responses with Photo-responsive, Ferulic Acid, and Nanopatterned Biomaterial Surfaces

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Authors

Karim, Sumaiya

Date

2025-02-28

Type

thesis

Language

eng

Keyword

Biomaterial , Lens , Cell response

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Abstract

Intraocular lenses (IOL) are polymer-based prosthetics used in cataract surgery to replace the diseased lenses in the eye. However after implantation, interactions of local lens epithelial cells (LECs) with the IOL can result in cellular epithelial-to-mesenchymal transition (EMT). The resulting phenotypic changes in LECs cause cell behaviours eventually leading to aggregate formation and lens wrinkling which form new vision issues called posterior capsular opacification (PCO). This research focuses on modifying the surfaces of IOL materials to modulate the behaviour of LECs. Coatings made of poly(methacrylic acid-co-isodecyl acrylate) (MAAcoIDA) and poly(methyl methacrylate-co-isodecyl acrylate) (MMcoIDA) were grafted with azobenzene using a spacer at the surface to study whether photo-responsive materials could modulate cell behaviour in situ. The immobilized azobenzene retained its ability to reversibly photoisomerize under 365 nm light and complex with β-cyclodextrin (β-CD). Cells grown on azo-modified MAAcoIDA (azoMAAcoIDA) in particular exhibited low viability and with UV exposure had low cell adhesion. Cells on β-CD-treated azoMAAcoIDA had differences in cell adhesion after UV treatments which indicate that β-CD decomplexation can modulate behaviors over time. The second part of this research developed copolymers consisting of 2-phenylethyl acrylate, and 2-phenylethyl methacrylate with different ratios of methacrylic acid which were modified at the surface with ferulic acid to modulate EMT in LECs. Cells grown on copolymer disks with low amounts of immobilized or solubilized ferulic acid were found to have reduced α-SMA protein expression when the cells were stimulated with TGF-β2. Lastly, the effect of 500, 900, and 1500 nm wave and peak patterns on IOL materials on the behaviour of LECs was investigated. After incubation of LEC on these patterns for 48 hours, the cell densities on 500 nm surfaces were decreased, which coincided with low cell clustering compared to larger patterns. This surface topography may have the potential to inhibit LEC adhesion when implemented on an IOL and thus prevent LEC adhesion and eventual PCO development. Collectively, this work suggests that these modified surfaces offer strategies for reducing LEC viability, adhesion, or EMT in LECs, important steps in PCO.

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