Enhanced Differentiation and Delivery of Mouse Retinal Progenitor Cells Using a Micropatterned Biodegradable Thin-Film Polycaprolactone Scaffold

Abstract

The deterioration of retinal tissue in advanced stages of retinitis pigmentosa and age-related macular degeneration and the lack of signaling cues for laminar regeneration are significant challenges highlighting the need for a tissue engineering approach to retinal repair. In this study, we fabricated a biodegradable thin-film polycaprolactone (PCL) scaffold with varying surface topographies using microfabrication techniques. Mouse retinal progenitor cells (mRPCs) cultured on PCL scaffolds exhibited enhanced potential to differentiate toward a photoreceptor fate in comparison to mRPCs cultured on control substrates, suggesting that PCL scaffolds are promising as substrates to guide differentiation of mRPCs toward a photoreceptor fate in vitro before transplantation. When cocultured with the retinal explants of rhodopsin null mice, mRPC/PCL constructs showed increased mRPC integration rates compared to directly applied dissociated mRPCs. Moreover, these mRPC/PCL constructs could be delivered into the subretinal space of rhodopsin null mice with minimal disturbance of the host retina. Whether cocultured with retinal explants or transplanted into the subretinal space, newly integrated mRPCs localized to the outer nuclear layer and expressed appropriate markers of photoreceptor fate. Thus, the PCL scaffold provides a platform to guide differentiation and organized delivery of mRPCs as a practical strategy to repair damaged retina.

Two-photon polymerization for production of human iPSC-derived retinal cell grafts

“…Although traditional microfabrication techniques offer precise control of pore size and distribution, resolution can limit pore size and spacing [17, 34–36]. In addition, even if one uses microfabrication to form sub-cellular structures, creating a truly three-dimensional scaffold with horizontal pores for nutrient diffusion in addition to vertical channels is challenging [37, 38]. Furthermore, the efficiency of traditional microfabrication is usually dependent on the use of silicon oxide or silicone rubber templates, meaning that one cannot easily adjust the overall scaffold design after they create the template.…”

3D Microfibrous Scaffolds Selectively Promotes Proliferation and Glial Differentiation of Adult Neural Stem Cells: A Platform to Tune Cellular Behavior in Neural Tissue Engineering

“…However, these cells have low integration efficiency into the brain circuitry, which may prevent long‐term positive outcomes. In recent years, studies have started focusing on using scaffolds in order to direct cells toward specific lineages . Additional studies have shown improvement of cell adhesion as well as differentiation of retinal progenitor cells seeded on polymeric scaffolds in a retinal degeneration model .…”

Tissue engineering of retina and Bruch’s membrane: a review of cells, materials and processes

“…As it has been stipulated that injected adherent cells cannot survive in the absence of a substrate,17 most implants employed the use of a resorbable scaffold to restitute cells into a tissue before transplanting it into the subretinal layer. Below are some of the methods reported, including cell sheet approach and scaffold-based approach.…”