Soy protein nanofiber scaffolds for uniform maturation of hiPSC-derived retinal pigment epithelium
Retinal pigment epithelial cells differentiated from human induced pluripotent stem cells (hiPSCs), called iRPE, are being explored as a cell-based therapy for the treatment of retinal degenerative diseases, especially age-related macular degeneration (AMD). The success of RPE implantation is believed to be linked to the use of biomimetic scaffolds that simulate Bruch's membrane and aid in its maturation and integration. Current practices widely utilize fibrous scaffolds from synthetic polymers, such as polycaprolactone (PCL), rather than from natural biomaterials. Here, we tested the hypothesis that naturally derived fibrous scaffolds, with their unique translational potential, can provide favorable conditions permissive for the maturation of iRPE in vitro. We show that the culture of iRPE on natural, soy protein-derived nanofibrous scaffolds match the results of similar cells cultured on synthetic PCL nanofibrous scaffolds. The mechanical properties of soy scaffolds better emulate the native Bruch's membrane, which would likely limit the foreign body reaction triggered by mismatch of host and biomaterial strength. Additionally, soy scaffolds exhibit unique biochemistry that improves biocompatibility and have tunable crosslinking to control degradation rates. Comparative transcriptome analysis demonstrates that iRPE maturation on nanofibrous scaffolds, either natural or synthetic, yielded more consistent outcomes than on other non-fibrous substrates. Taken together, our studies suggest that the maturation of cultured RPE for subsequent clinical applications will benefit from the use of nanofibrous scaffolds derived from natural proteins. Overall design: Human iPSC derived retinal pigment epithelium (RPE) were diffentiated on laminin-coated chamber slides, Transwell™ only, electrospun soy scaffolds or polycaprolactone (PCL) scaffolds. Differentiation experiments were performed in triplicate and RNA harvested for RNA-seq library construction.