Engineered micro-structured biomimetic material for modelling the outer blood-retinal barrier

The outer blood-retinal barrier (oBRB) is compromised in several retinal pathologies, such as age-related macular degeneration affecting over 200 million people worldwide. This 200-350 microm thick tissue includes the retinal pigment epithelium (RPE), the Bruch's membrane, and the vascularized choroid supplying the outer retina. Degeneration of the RPE and/or choroid leads to photoreceptor loss and, ultimately, blindness. Current in vitro co-culture oBRB models developed to better understand the diseases and to propose therapeutic alternatives are often simplistic, focusing on 2D cultures, or face limitations including non-physiological dimensions or low throughput. This study presents an innovative scaffold-driven approach to model the oBRB using a polysaccharide membrane engineered by freeze-drying. Our specific protocol allowed to mimic the oBRB structure, within physiological dimensions, generating a non-porous surface to culture the hiPSC-derived RPE monolayer, and an internal 3D porous structure for the choroidal network. Results showed that the inner porous structure promoted physiological self-organization of endothelial cells and pericytes. Our single-piece functional material allowed the cultivation of both RPE and choroidal compartments in close proximity, favoring cellular interactions, while maintaining them in their designated locations. This cyto-compatible, easy-to-use, and off-the-shelf membrane, produced at large amounts and low costs, provides a physiologically relevant biomaterial for oBRB tissue modelling.