Biofunctionalized gelatin hydrogels support development and maturation of iPSC-derived cortical organoids
Andrew Kjar, Mia R Haschert, José C. Zepeda, Aaron B. Simmons, A K Yates, Daniel Chavarría, Melanie Fernandez, Gabriella L. Robertson, Adam M Abdulrahman, Hyosung Kim, Nicole T. Marguerite, Rachel K Moen, Lauren E. Drake, Corinne W. Curry, Brian J. O’Grady, Vivian Gama, Ken S. Lau, Brad A. Grueter, Jonathan M. Brunger, Ethan S. Lippmann
Abstract
Human neural organoid models have become an important tool for studying neurobiology. However, improving the representativeness of neural cell populations in such organoids remains a major effort. In this work, we compared Matrigel, a commercially available matrix, to a neural cadherin (N-cadherin) peptide-functionalized gelatin methacryloyl hydrogel (termed GelMA-Cad) for culturing cortical neural organoids. We determined that peptide presentation can tune cell fate and diversity in gelatin-based matrices during differentiation. Of particular note, cortical organoids cultured in GelMA-Cad hydrogels mapped more closely to human fetal populations and produced neurons with more spontaneous excitatory postsynaptic currents relative to Matrigel. These results provide compelling evidence that matrix-tethered signaling peptides can influence neural organoid differentiation, opening an avenue to control stem cell fate. Moreover, outcomes from this work showcase the technical utility of GelMA-Cad as a simple and defined hydrogel alternative to Matrigel for neural organoid culture.