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University of Hong Kong
Adv. Healthc. Mater., May 11 2026, | https://doi.org/10.1002/adhm.202504842
Flash Assembloids: A Rapid Biofabrication of a Platform for Modeling Early Glioblastoma Invasion at the Glioblastoma-Brain Organoid Interfaces
Chao Liang 1 †, Henry Robert Howard 2 3 4 †, Shihui Chen 2 3 5 †, Won-Young Choi 6 †, Summer Cao 2 3 4, Arthur Chien 7, Kevin Zou 2 3 4, Michael Kassiou 8, Fabien Delerue 9, Ho Sang Jung 10, Yeonju Park 11, Young Mee Jung 11, Yong-Dae Kwon 12, Karrie M Kiang 13, Gilberto Ka-Kit Leung 13, Ryohichi Sugimura 14, Ann-Na Cho 2 3 4 5 *, Sang Jin Lee 1 15 *
1Biofunctional Materials Division of Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong, SAR, China.
2School of Biomedical Engineering, Faculty of Engineering, The University of Sydney, Darlington, New South Wales, Australia.
3The University of Sydney Nano Institute (Sydney Nano), The University of Sydney, Camperdown, New South Wales, Australia.
4Brain and Mind Centre, The University of Sydney, Camperdown, New South Wales, Australia.
5Centre for Drug Discovery and Innovation, The University of Sydney, Camperdown, New South Wales, Australia.
6Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
7The Microscopy Unit, Faculty of Science and Engineering, Macquarie University, Sydney, New South Wales, Australia.
8School of Chemistry, The University of Sydney, Sydney, New South Wales, Australia.
9Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
10School of Biomedical Engineering, Korea University, Seoul, Republic of Korea.
11Department of Chemistry, Institute for Molecular Science and Fusion Technology, and Kangwon Radiation Convergence Research Support Center, Kangwon National University, Chuncheon, Republic of Korea.
12Department of Oral & Maxillofacial Surgery, College of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
13Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
14School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, SAR, People's Republic of China.
15College of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, Republic of Korea.
2School of Biomedical Engineering, Faculty of Engineering, The University of Sydney, Darlington, New South Wales, Australia.
3The University of Sydney Nano Institute (Sydney Nano), The University of Sydney, Camperdown, New South Wales, Australia.
4Brain and Mind Centre, The University of Sydney, Camperdown, New South Wales, Australia.
5Centre for Drug Discovery and Innovation, The University of Sydney, Camperdown, New South Wales, Australia.
6Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
7The Microscopy Unit, Faculty of Science and Engineering, Macquarie University, Sydney, New South Wales, Australia.
8School of Chemistry, The University of Sydney, Sydney, New South Wales, Australia.
9Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
10School of Biomedical Engineering, Korea University, Seoul, Republic of Korea.
11Department of Chemistry, Institute for Molecular Science and Fusion Technology, and Kangwon Radiation Convergence Research Support Center, Kangwon National University, Chuncheon, Republic of Korea.
12Department of Oral & Maxillofacial Surgery, College of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
13Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
14School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, SAR, People's Republic of China.
15College of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, Republic of Korea.
†Chao Liang, Henry Robert Howard, Shihui Chen, and Won-Young Choi contributed equally to this work.
*Corresponding authors: correspondence to Ann-Na Cho or Sang Jin Lee
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.
논문정보
- Research article
- 2026년 05월 (BRIC 등록일 2026-05-13)
- 국내(교신)+국외 연구진
- 바이오·의료융합 > 바이오·의료융합 기타
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