TY - JOUR
KW - diffusion
KW - drug response
KW - Electrophysiology
KW - organoids
KW - perfusion
KW - scaffolds
KW - vascular networks
AU - Hongwei Cai
AU - Chunhui Tian
AU - Lei Chen
AU - Yang Yang
AU - Alfred Xuyang Sun
AU - Kyle McCracken
AU - Jason Tchieu
AU - Mingxia Gu
AU - Ken Mackie
AU - Feng Guo
AB - Organoids, 3D organ-like tissue cultures derived from stem cells, show promising potential for developmental biology, drug discovery, and regenerative medicine. However, the function and phenotype of current organoids, especially neural organoids, are still limited by insufficient diffusion of oxygen, nutrients, metabolites, signaling molecules, and drugs. Herein, we present vascular network-inspired diffusible (VID) scaffolds to mimic physiological diffusion physics for generating functional organoids and phenotyping their drug response. Specifically, the VID scaffolds, 3D-printed meshed tubular channel networks, successfully engineer human midbrain organoids almost without necrosis and hypoxia in commonly used well plates. Compared with conventional organoids, these engineered organoids develop more physiologically relevant features and functions, including midbrain-specific identity, oxygen metabolism, neuronal maturation, and network activity. Moreover, these engineered organoids also better recapitulate pharmacological responses, such as neural activity changes to fentanyl exposure, compared with conventional organoids with significant diffusion limits. This platform may provide insights for organoid development and therapeutic innovation.
BT - Cell Stem Cell
DA - 2025-03-17
DO - 10.1016/j.stem.2025.02.010
N2 - Organoids, 3D organ-like tissue cultures derived from stem cells, show promising potential for developmental biology, drug discovery, and regenerative medicine. However, the function and phenotype of current organoids, especially neural organoids, are still limited by insufficient diffusion of oxygen, nutrients, metabolites, signaling molecules, and drugs. Herein, we present vascular network-inspired diffusible (VID) scaffolds to mimic physiological diffusion physics for generating functional organoids and phenotyping their drug response. Specifically, the VID scaffolds, 3D-printed meshed tubular channel networks, successfully engineer human midbrain organoids almost without necrosis and hypoxia in commonly used well plates. Compared with conventional organoids, these engineered organoids develop more physiologically relevant features and functions, including midbrain-specific identity, oxygen metabolism, neuronal maturation, and network activity. Moreover, these engineered organoids also better recapitulate pharmacological responses, such as neural activity changes to fentanyl exposure, compared with conventional organoids with significant diffusion limits. This platform may provide insights for organoid development and therapeutic innovation.
PY - 2025
T2 - Cell Stem Cell
TI - Vascular network-inspired diffusible scaffolds for engineering functional midbrain organoids
UR - https://www.sciencedirect.com/science/article/pii/S1934590925000499
Y2 - 2025-04-30
SN - 1934-5909
ER -