Abstract
Purpose:
Patients with advanced stages of retinal degenerative disease would benefit greatly if a means could be devised for transplanting functional cells into the injured retina. Although bolus sub-retinal cell injections have been shown to restore function to retinas with early stages of disease, this success translates poorly to more advanced disease in which there is a lack of structural support for the integrating cells. Stem cell scaffolds can be used to provide this support, but the effects of the physical properties of these scaffolds (i.e. their nanostructure) on the transplanted cells is poorly understood.
Methods:
Nano-porous cell scaffolds were synthesized by lyotropic liquid crystalline (LLC) templating of photopolymerizable poly(ethylene glycol) pre-polymers. Morphology was characterized using scanning electron microscopy (SEM), small-angle x-ray scattering (SAXS), and polarized light microscopy (PLM). Surfactant removal and swelling were both examined gravimetrically. The effect of nanostructure on the interaction between the cells and the scaffolds was investigated by seeding the materials with murine induced pluripotent stem (MiPS) cells, and monitoring their growth and differentiation with SEM and immunohistochemsitry.
Results:
Polymers templated with 30 wt% DTAB, an ionic surfactant, manifested scattering peaks, birefringence, and porosity when examined using small-angle x-ray scattering, polarized light microscopy, and SEM, respectively, all of which are indicators of nanostructure. This presence of nanostructure improved the diffusion properties of the material and also influenced the growth and differentiation of cells. The optimized materials produced were shown to support the differentiation of induced pluripotent stem cells to mature retinal cell types.
Conclusions:
Nanostructure of photopolymers plays an important role in cell/material interactions and can be successfully manipulated to meet the needs of retinal transplant applications. Development of a material that is biocompatible, implantable, and able to encourage growth and differentiation of mature retinal cell types would be a major step toward the successful replacement of lost photoreceptor cells and restoration of retinal function in patients suffering from retinal degenerative disease.
Keywords: 687 regeneration •
500 differentiation •
721 stem cells