Biomaterial scaffolds for retinal repair: The synthesis and characterization of three poly(ethylene glycol)/poly(L-lysine) hydrogels and their influence on neural progenitor cells

Vision loss resulting from diseases such as retinitis pigmentosa and age-related macular degeneration affects millions worldwide. These diseases result in the degeneration of the retinal pigmented epithelium and photoreceptor cell layer, cells that are critical to our ability to process visual light. However, both patterns of degeneration spare many of the inner neurons of the retina that transport visual signals from the photoreceptor layer to the optic nerve and brain. A promising treatment for these diseases is a cell therapy that would deliver healthy retinal cells that could synapse with the remaining neurons. Neural progenitor cells (NPCs) are specific to the central nervous system and demonstrate excellent integration into retina and differentiation into morphologies of retinal cell types. Biomaterial scaffolds may be a critical component of retinal cell therapies due to their ability to promote survival, differentiation and organization to transplanted cells. This dissertation describes the development of poly(ethylene glycol) (PEG)/poly(L-lysine) (PLL) hydrogels by three fabrication methods: chemical crosslinking, photopolymerization and freeze-dried preparation and the effects of these gels on the behavior of NPCs.;A library of chemically crosslinked PEG/PLL hydrogels was developed to examine the relationship between materials properties and progenitor cell behavior. A subset of gels within the library promoted the migration and neuronal differentiation of NPCs. Hydrogels that exhibited high migration had elastic moduli between 3,500--5,500 Pa, amine concentrations ranging from 0--3.0 micromoles/mg and contained mid-molecular weight PLL (70--150 kDa). We have developed a photopolymerized hydrogel composed of macromers of PEG bound to PLL that supports NPC survival and directs neuronal differentiation. Photopolymerized gels can be cured in situ and may provide a minimally invasive way to deliver NPCs.;Additionally, we have developed a freeze-dried PEG/PLL gel containing pores aligned normal to the gel surface with an average diameter of 137 microm +/- 32 microm. These freeze-dried gels direct the differentiation of NPCs into astrocyte and neuronal cell types. This research examines the relationship between materials and progenitor cell behavior and represents the first steps towards the development of a hydrogel scaffold for progenitor cell delivery to the subretinal space.