Microdevice-based cell therapy for age-related macular degeneration

This chapter reports the application of a micromachined parylene-C device as an artificial Bruch's membrane for the stem cell-based therapy of age-related macular degeneration. The feasibility of parylene-C as a substitute substrate material is demonstrated by evaluating the permeability of membranes of submicron thicknesses. It has been found that parylene-C membranes thinner than 0.3 µm possess similar molecular weight exclusion limit and nutrient diffusion flux to that of the healthy human Bruch's membrane. This conclusion is further validated by the in vitro perfusion cell viability test. Since the submicron parylene-C itself is difficult to handle, we design a mesh-supported submicron parylene membrane (MSPM) to provide sufficient mechanical support. This MSPM can support the growth of retinal pigment epithelial (RPE) cells in a monolayer with well-polarized morphology. Human embryonic stem cell-derived H9-RPE cells are cultured in vitro on the MSPM for one month before the implantation of the MSPM into the rat's retina. To facilitate the surgical implantation, a parylene-C/SU-8 hybrid microfluidic device is designed as an inserter. Histological studies with hematoxylin-eosin staining and immunofluorescence staining show that the implanted RPE cells adhere well to the artificial Bruch's membrane and are able to maintain high viability and normal morphology in vivo.