Injectable ultrathin porous membranes harnessing shape memory polymers for retinal tissue engineering†

Abstract

Age-related macular degeneration (AMD) is a leading cause of vision loss, characterized by the progressive degeneration of retinal cells, particularly retinal pigment epithelial (RPE) cells. Conventional treatments primarily focus on slowing disease progression without providing a cure. Recent advances in tissue engineering and cell-based therapies offer promising avenues for regenerating retinal tissue and restoring vision. In this study, we developed ultrathin, nanoporous membrane scaffolds designed to mimic Bruch's membrane (BrM) for RPE cell transplantation using vapor-induced phase separation. These scaffolds, fabricated from a blend of poly(L-lactide-co-ε-caprolactone) (PLCL) and poly(lactic-co-glycolic acid) (PLGA), exhibited favorable topography, biocompatibility, and shape-memory properties. In vitro experiments confirmed that the nanoporous topography effectively supports the formation of RPE monolayers with intact tight junctions. Additionally, the shape-memory characteristic enables the membrane to self-expand at body temperature (37 °C), facilitating minimally invasive delivery via injection. ARPE-19 cell-attached nanothin membranes successfully demonstrated shape-recovery properties and were deliverable through a catheter in an ex vivo model. Our findings suggest that the developed scaffolds provide a promising approach for retinal tissue engineering and could significantly contribute to advanced treatments for AMD and other retinal degenerative diseases.