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Flash Assembloids: A Rapid Biofabrication of a Platform for Modeling Early Glioblastoma Invasion at the Glioblastoma-Brain Organoid Interfaces.

Overview

Authors: Chao Liang1, Henry Robert Howard2,3,4, Shihui Chen2,3,5, Won‐Young Choi6, Summer Cao2,3,4, Arthur Chien7, Kevin Zou2,3,4, Michael Kassiou8, Fabien Delerue9, Ho Sang Jung10, Yeonju Park11, Young Mee Jung11, Yong‐Dae Kwon12, Karrie M Kiang13, Gilberto Ka‐Kit Leung13, Ryohichi Sugimura14, Ann‐Na Cho2,3,4,5, Sang Jin Lee15,1
ORCID iDs: Chao Liang, Henry Robert Howard, Shihui Chen, Arthur Chien, Ryohichi Sugimura, Ann‐Na Cho, Sang Jin Lee
15 affiliations
  1. Biofunctional Materials Division of Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong, SAR, China
  2. School of Biomedical Engineering, Faculty of Engineering, The University of Sydney, Darlington, New South Wales, Australia
  3. The University of Sydney Nano Institute (Sydney Nano), The University of Sydney, Camperdown, New South Wales, Australia
  4. Brain and Mind Centre, The University of Sydney, Camperdown, New South Wales, Australia
  5. Centre for Drug Discovery and Innovation, The University of Sydney, Camperdown, New South Wales, Australia
  6. Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee, USA
  7. The Microscopy Unit, Faculty of Science and Engineering, Macquarie University, Sydney, New South Wales, Australia
  8. School of Chemistry, The University of Sydney, Sydney, New South Wales, Australia
  9. Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  10. School of Biomedical Engineering, Korea University, Seoul, Republic of Korea
  11. Department of Chemistry, Institute for Molecular Science and Fusion Technology, and Kangwon Radiation Convergence Research Support Center, Kangwon National University, Chuncheon, Republic of Korea
  12. Department of Oral & Maxillofacial Surgery, College of Dentistry, Kyung Hee University, Seoul, Republic of Korea
  13. Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China
  14. School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, SAR, People's Republic of China
  15. College of Dentistry, Kyung Hee University, 26 Kyungheedae‐ro, Dongdaemun‐gu, Seoul, Republic of Korea
Institutions: University of Hong Kong (Hong Kong SAR China); The University of Sydney (Australia); University of Tennessee Health Science Center (United States); Macquarie University (Australia); The University of Texas MD Anderson Cancer Center (United States); Korea University (South Korea); Kangwon National University (South Korea); Kyung Hee University (South Korea); Kyung Hee University Dental Hospital (South Korea)
Journal: Advanced healthcare materials, volume 15, issue 33, article e04842
Dates: received 30 September 2025; accepted 30 April 2026; published online 11 May 2026; in print 4 September 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1002/adhm.202504842 · PMID 42116568 · PMCID PMC13542853 · OpenAlex W7160930831
Open access: hybrid, a free copy (OpenAlex)
Status: data only
Categories: human (organism), mouse (organism), other condition (population)
Methods: Preprocessing, Statistics, Spectral & time-frequency, Evoked potentials, fMRI & imaging
Keywords: glioblastoma, invasiveness, tumor‐host interactions, tumor extracellular matrix, organoid fabrication
MeSH: Brain*, Brain Neoplasms*, Glioblastoma*, Organoids*, Alginates, Animals, Cell Adhesion, Cell Line, Tumor, Humans, Mice, Neoplasm Invasiveness, Signal Transduction (* major topic)
Topic: Cell Adhesion Molecules Research (Immunology and Allergy, Medicine), according to OpenAlex
Funding: National Health and Medical Research Council Emerging Leadership 1 Fellow (2024/GNT2033108); Centre for Drug Discovery Innovation; Sydney Horizon Fellowship; Australian Academy of Technology and Engineering (ATSE) Global Connections Fund (2025-A.N.C 77-AU); Brain and Mind Centre/Engagement Collaborative Grants; National Research Foundation of Korea funded by the Ministry of Science and ICT (RS-2024-00338610); Technology Development Program funded by the Ministry of SMEs and Startups (MSS, Korea) (RS-2024-00512145); Sydney Nano Institute Kickstarter
Citations: not cited yet (Europe PMC); 95 references in the paper

Abstract

Glioblastoma (GBM) remains one of the most aggressive brain malignancies, characterized by rapid infiltration, therapeutic resistance, and dismal prognosis. Modeling GBM invasion in physiologically relevant systems has been hindered by the lack of reproducible platforms. Here, we present a bioengineered assembloid (ASM) system that integrates GBM cells encapsulated in self‐degradable 5% oxidized alginate microgel (5OA) with dorsal forebrain organoids (DOs) to recapitulate early tumor‐host interactions during glioblastoma invasion toward the brain. Live‐cell imaging revealed GBM self‐aggregation, leading to increased recruitment and invasion at the DO boundary, accompanied by strong cell‐cell adhesion, nuclear compaction, and the infiltration fronts enriched in SOX2+/Vimentin+ tumor populations. Transcriptomic profiling demonstrated upregulation of adhesion, integrin clustering, and mechanosensing‐associated genes, alongside downregulation of neuronal differentiation pathways, indicating a dual invasion and host suppression strategy. Comparative analyses of GBM‐only constructs and DO‐GBM ASMs revealed elevated expression of laminin subunits and enrichment of invasion‐associated pathways, including PI3K‐AKT‐mTOR and TGF‐β signaling, reflecting a shift toward an invasive state at the transcriptomic level. In vivo implantation of ASMs confirmed aggressive GBM infiltration and niche remodeling, highlighting the translational relevance. These findings suggest that it recapitulates the structural, molecular, and functional hallmarks of GBM invasion and tumor‐driven remodeling of the host brain microenvironment.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

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Data

Datasets cited

Data Availability Statement

The datasets supporting the conclusions of this article are available in the GEO database (GSE325111).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Publisher: n/a → Wiley

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 18 authors, 5 keywords, 12 MeSH terms, 8 funders, 92 references.

Cite

This paper

Liang, C., Howard, H. R., Chen, S., Choi, W., Cao, S., Chien, A., Zou, K., Kassiou, M., Delerue, F., Jung, H. S., Park, Y., Jung, Y. M., Kwon, Y., Kiang, K. M., Leung, G. K., Sugimura, R., Cho, A., & Lee, S. J. (2026). Flash Assembloids: A Rapid Biofabrication of a Platform for Modeling Early Glioblastoma Invasion at the Glioblastoma-Brain Organoid Interfaces. Advanced healthcare materials, 15(33), e04842. https://doi.org/10.1002/adhm.202504842

BibTeX

@article{liang2026flash,
author = {Liang, Chao and Howard, Henry Robert and Chen, Shihui and Choi, Won‐Young and Cao, Summer and Chien, Arthur and Zou, Kevin and Kassiou, Michael and Delerue, Fabien and Jung, Ho Sang and Park, Yeonju and Jung, Young Mee and Kwon, Yong‐Dae and Kiang, Karrie M and Leung, Gilberto Ka‐Kit and Sugimura, Ryohichi and Cho, Ann‐Na and Lee, Sang Jin},
title = {{Flash Assembloids: A Rapid Biofabrication of a Platform for Modeling Early Glioblastoma Invasion at the Glioblastoma-Brain Organoid Interfaces}},
journal = {Advanced healthcare materials},
year = {2026},
month = may,
volume = {15},
number = {33},
pages = {e04842},
publisher = {Wiley},
issn = {2192-2640},
doi = {10.1002/adhm.202504842},
url = {https://doi.org/10.1002/adhm.202504842},
pmid = {42116568},
pmcid = {PMC13542853}
}

RIS

TY - JOUR
AU - Liang, Chao
AU - Howard, Henry Robert
AU - Chen, Shihui
AU - Choi, Won‐Young
AU - Cao, Summer
AU - Chien, Arthur
AU - Zou, Kevin
AU - Kassiou, Michael
AU - Delerue, Fabien
AU - Jung, Ho Sang
AU - Park, Yeonju
AU - Jung, Young Mee
AU - Kwon, Yong‐Dae
AU - Kiang, Karrie M
AU - Leung, Gilberto Ka‐Kit
AU - Sugimura, Ryohichi
AU - Cho, Ann‐Na
AU - Lee, Sang Jin
TI - Flash Assembloids: A Rapid Biofabrication of a Platform for Modeling Early Glioblastoma Invasion at the Glioblastoma-Brain Organoid Interfaces
T2 - Advanced healthcare materials
J2 - Adv Healthc Mater
PY - 2026
DA - 2026/05/11
VL - 15
IS - 33
SP - e04842
SN - 2192-2640
PB - Wiley
DO - 10.1002/adhm.202504842
UR - https://doi.org/10.1002/adhm.202504842
LA - en
ER -

CSL-JSON

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