Spatial engineering of posterior signaling centers in cerebral organoids via controlled morphogen exposure within hydrogels
Abstract
Cerebral cortex organoids are powerful in vitro models that recapitulate key features of human development. However, conventional methods produce cortical organoids with spontaneous, spatially disorganized cortical regions due to limited control over morphogen distribution within local environments. Here, we present a spatially engineered hydrogel platform that drives localized posterior organizer formation in cortical organoids through controlled, localized exposure to morphogens. Using a combination of bulk photopolymerization, thermal crosslinking, and digital light processing (DLP) approaches, we fabricated hydrogels with stiffness-controlled layers that preferentially deliver morphogens to one side of the organoid, selectively inducing posterior organizer formation on the exposed face. We further validated this platform by delivering fluorescently tagged dextran, used as molecular weight-matched model morphogens, to visualize spatiotemporal delivery dynamics at the organoid interface. As a proof of principle, we also demonstrated that DLP fabrication enables the printing of dual morphogen hubs, serving as a model for establishing two opposing gradients within a single organoid. Together, this hydrogel platform enables systematic spatial patterning of cell populations in organoids, more faithfully recapitulating the spatial organization and cellular diversity of native tissues and advancing higher-fidelity models for studying human development and disease.
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BibTeX
@misc{jeong2026spatial,
title = {{Spatial engineering of posterior signaling centers in cerebral organoids via controlled morphogen exposure within hydrogels}},
author = {H. Jeong and H. Ozaki and Y.-C. Tsai and C. Nie and S. R. Foust and K. Shiraiwa and Z. Zhuang and D. Miller and M. J. M. Noh and J. K. Dalal and A. G. Salem and C. H. Vu and A. Mohraz and M. Watanabe and H. A. M. Ardona},
howpublished = {bioRxiv},
year = {2026},
month = jun,
doi = {10.64898/2026.06.02.729607},
url = {https://www.biorxiv.org/content/10.64898/2026.06.02.729607v2},
note = {Public domain},
}
RIS
TY - UNPB
TI - Spatial engineering of posterior signaling centers in cerebral organoids via controlled morphogen exposure within hydrogels
AU - H. Jeong
AU - H. Ozaki
AU - Y.-C. Tsai
AU - C. Nie
AU - S. R. Foust
AU - K. Shiraiwa
AU - Z. Zhuang
AU - D. Miller
AU - M. J. M. Noh
AU - J. K. Dalal
AU - A. G. Salem
AU - C. H. Vu
AU - A. Mohraz
AU - M. Watanabe
AU - H. A. M. Ardona
PY - 2026
DA - 2026/06/02
PB - bioRxiv
DO - 10.64898/2026.06.02.729607
UR - https://www.biorxiv.org/content/10.64898/2026.06.02.729607v2
AB - Cerebral cortex organoids are powerful in vitro models that recapitulate key features of human development. However, conventional methods produce cortical organoids with spontaneous, spatially disorganized cortical regions due to limited control over morphogen distribution within local environments. Here, we present a spatially engineered hydrogel platform that drives localized posterior organizer formation in cortical organoids through controlled, localized exposure to morphogens. Using a combination of bulk photopolymerization, thermal crosslinking, and digital light processing (DLP) approaches, we fabricated hydrogels with stiffness-controlled layers that preferentially deliver morphogens to one side of the organoid, selectively inducing posterior organizer formation on the exposed face. We further validated this platform by delivering fluorescently tagged dextran, used as molecular weight-matched model morphogens, to visualize spatiotemporal delivery dynamics at the organoid interface. As a proof of principle, we also demonstrated that DLP fabrication enables the printing of dual morphogen hubs, serving as a model for establishing two opposing gradients within a single organoid. Together, this hydrogel platform enables systematic spatial patterning of cell populations in organoids, more faithfully recapitulating the spatial organization and cellular diversity of native tissues and advancing higher-fidelity models for studying human development and disease.
ER -