TY - JOUR
KW - Apical-out airway organoid (AoAO)
KW - Ciliary motility
KW - cryopreservation
KW - Decellularized extracellular matrix (dECM)
KW - Mucociliary differentiation
KW - Swarm analysis
AU - Zhuowei Gong
AU - Dhruv Bhattaram
AU - Laura Porritt
AU - Kian Golestan
AU - Amir Barati Farimani
AU - Bin Deng
AU - Amy L. Ryan
AU - Daniel J. Weiss
AU - Xi Ren
AB - The airway epithelium is a dynamic barrier that interfaces with the external environment and internal matrix along its apicobasal axis. To recapitulate this spatial organization and associated cell-ECM interactions in an organoid format, we present the decellularized extracellular matrix-incorporated Apical-out Airway Organoid (dECM-AoAO), which integrates basolateral matrix cues through the incorporation of human lung dECM microparticles (dECM-MPs), while maintaining direct apical exposure to the exterior. Compared to ECM-free AoAOs, dECM incorporation diversifies lineage distribution, more closely recapitulating native epithelial composition and responsiveness to pathogenic stimulation. Harnessing dECM-AoAO locomotion driven by outward-facing ciliary beating, we developed an experimental and computational pipeline for batch analysis of organoid motility as a functional readout of ciliary activity. Furthermore, dECM-AoAOs are compatible with cryopreservation, retaining viability, lineage composition, and ciliary function upon revival. Together, this work establishes the dECM-AoAO as a physiologically relevant model system for investigating epithelial-ECM crosstalk during airway homeostasis, pathogenesis, and injury responses.
BT - Biomaterials
DA - 2026-08-01
DO - 10.1016/j.biomaterials.2026.124084
N2 - The airway epithelium is a dynamic barrier that interfaces with the external environment and internal matrix along its apicobasal axis. To recapitulate this spatial organization and associated cell-ECM interactions in an organoid format, we present the decellularized extracellular matrix-incorporated Apical-out Airway Organoid (dECM-AoAO), which integrates basolateral matrix cues through the incorporation of human lung dECM microparticles (dECM-MPs), while maintaining direct apical exposure to the exterior. Compared to ECM-free AoAOs, dECM incorporation diversifies lineage distribution, more closely recapitulating native epithelial composition and responsiveness to pathogenic stimulation. Harnessing dECM-AoAO locomotion driven by outward-facing ciliary beating, we developed an experimental and computational pipeline for batch analysis of organoid motility as a functional readout of ciliary activity. Furthermore, dECM-AoAOs are compatible with cryopreservation, retaining viability, lineage composition, and ciliary function upon revival. Together, this work establishes the dECM-AoAO as a physiologically relevant model system for investigating epithelial-ECM crosstalk during airway homeostasis, pathogenesis, and injury responses.
PY - 2026
EP - 124084
T2 - Biomaterials
TI - Recapitulating apicobasal tissue polarity in extracellular matrix-incorporated airway organoids
UR - https://www.sciencedirect.com/science/article/pii/S0142961226001080
VL - 331
Y2 - 2026-03-12
SN - 0142-9612
ER -