A microfabricated 3-D stem cell delivery scaffold for retinal regenerative therapy

Abstract

Diseases affecting the retina, such as Age-related Macular Degeneration (AMD) and Retinitis Pigmentosa (RP), result in the degeneration of the photoreceptor cells and can ultimately lead to blindness in patients. There is currently no cure for AMD or RP, and only a few methods exist for slowing the progression of these diseases. Although there has been much recent headway in cell replacement therapy to restore vision loss, a number of challenges still remain. More specifically, there is a need for the development of a device that can deliver a large number of cells to the posterior segment of the eye, while promoting cell survival, differentiation and integration into the retina following transplantation. This research focuses on designing a device to meet these demands and improve the vision of those afflicted with blinding diseases. The specific hypothesis behind the proposed research is that a MEMS-based strategy to engineer a device can provide precisely defined spatial and chemical cues to influence retinal progenitor cells (RPCs) attachment, promote differentiation, and provide physical guidance in a more normal anatomical organization for their integration as neurosensory retina after transplantation to the subretinal space. Therefore, the specific aims of this research are to design, fabricate, and evaluate in vitro a novel ultrathin 3-D device made of polycaprolactone (PCL) for retinal cell replacement synthesized by the stacking, aligning, and bonding of three uniquely designed layers.

(cont.)Photolithography, standard replica molding, and soft lithography techniques are used to fabricate the device elements. The 3-D device is designed with a defined cage structure to encapsulate a large number of cells. Another layer of the design allows for unidirectional cell migration out of one end into the subretinal space with the aid of contact guidance ridges. The third design layer allows for nutrient infiltration from the retinal pigment epithelium into the cell cages. The ultimate goal is to provide an environment compatible with the normal retinal tissue and conducive to the formation of functional synapses under the appropriate conditions, thereby restoring proper vision. With demonstration of efficacy and cell retention in vitro, the scaffold has the potential to reverse retinal degeneration due to disease or trauma and improve retinal function and integrity in vivo.