Novel decellularized liver matrix-alginate hybrid gel beads for the 3D culture of hepatocellular carcinoma cells
Abstract
Developing reliable three-dimensional (3D) cell culture systems that can mimic native tumor microenvironments is necessary for investigating the mechanism of hepatocellular carcinoma (HCC) metastasis and screen therapeutic drugs. In the present study, we developed decellularized liver matrix-alginate (DLM-ALG) hybrid gel beads. DLM powder was prepared by optimized decellularization methods and liquid nitrogen grinding. DLM-ALG beads were generated by dropping alginate solution containing DLM powder into a gelling bath. DLM powder concentration in alginate solution was ≤1% (w/v) and had no effect on the sphericity and mechanical stability of the beads. In addition, HCCLM3 cells cultured in 1% (w/v) DLM-ALG beads presented gradually enhanced viability during in vitro culture. The protein expression of urokinase plasminogen activator system and activity of matrix metalloproteinases (MMPs) of HCCLM3 cells, including MMP2 and MMP9, were more significantly promoted in DLM-ALG beads compared with that in conventional ALG beads without DLM powder. Moreover, the dose-dependent increase in HCCLM3 cell MMP activities was observed along with the DLM powder concentration in 0.5% and 1% DLM-ALG groups. Therefore, DLM-ALG beads might serve as a novel 3D culture system for exploring the mechanisms of HCC metastasis and screening therapeutic drugs.
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Immersion/agitation was preferred due to the capability to process large quantities of diced or chopped tissues.
“Immersion was cited the most often (53 articles) and was given preference due to the capability to process large quantities of diced or chopped tissues [38,63].”
Immersion/agitation was the most often cited decellularization method (53 articles).
“Immersion was cited the most often (53 articles) and was given preference due to the capability to process large quantities of diced or chopped tissues [38,63].”
Cites
Unger, C., Kramer, N., Walzl, A., Scherzer, M., Hengstschläger, M., & Dolznig, H. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.10.015 · Cited by 158 · see citing works
Mechanostructure and composition of highly reproducible decellularized liver matrices
Mattei, G., Di Patria, V., Tirella, A., Alaimo, A., Elia, G., Corti, A., Paolicchi, A., & Ahluwalia, A. (2014) · Acta Biomaterialia · doi:10.1016/j.actbio.2013.10.023 · Cited by 78 · see citing works
Solubilized liver extracellular matrix maintains primary rat hepatocyte phenotype <i>in‐vitro</i>
Loneker, A. E., Faulk, D. M., Hussey, G. S., D'Amore, A., & Badylak, S. F. (2016) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.35636 · Cited by 75 · see citing works
Mazzitelli, S., Luca, G., Mancuso, F., Calvitti, M., Calafiore, R., Nastruzzi, C., Johnson, S., & Badylak, S. F. (2011) · Acta Biomaterialia · doi:10.1016/j.actbio.2010.10.005 · Cited by 41 · see citing works
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Tao, M., Ao, T., Mao, X., Yan, X., Javed, R., Hou, W., Wang, Y., Sun, C., Lin, S., Yu, T., et al. (2021) · Bioactive Materials · doi:10.1016/j.bioactmat.2021.02.010 · Cited by 119 · see citing works
Engineering Liver Microtissues for Disease Modeling and Regenerative Medicine
Huang, D. (., Gibeley, S. B., Xu, C., Xiao, Y., Celik, O., Ginsberg, H. N., & Leong, K. W. (2020) · Advanced Functional Materials · doi:10.1002/adfm.201909553 · Cited by 65 · see citing works
Majidi, Z., Sarvi, M. M., Rajabi, M. A., Firouzian, H., Seyhoun, I., & Majidi Zolbin, M. (2026) · Regenerative Therapy · doi:10.1016/j.reth.2025.11.006 · Cited by 5 · see citing works
- Authors
- Sun, D., Liu, Y., Wang, H., Deng, F., Zhang, Y., Zhao, S., Ma, X., Wu, H., & Sun, G.
- Affiliations
- Dalian Institute of Chemical Physics (CN)
- Dalian University of Technology (CN)
- Corresponding author
- Liu, Yang
- Sun, Guangwei
- Venue
- International Journal of Biological Macromolecules
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 109
- Pages
- 1154-1163
- ISSN
- 0141-8130 (ISSN-L)
- OpenAlex
- W2769526669
- Cited by
- 45
- References
- 4
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 8 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 9 · 2019: 5
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Biological Macromolecules (publishedVersion)
- PubMed (publishedVersion)
- Dalian Institute of Chemical Physics, CAS Institutional Repository (submittedVersion)
- Funders
- National Natural Science Foundation of China (31470944)
- Dalian Institute of Chemical Physics (DICP ZZBS201606)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- alginate beads, hepatocellular carcinoma, 3D cell culture, tumor microenvironment, metastasis, urokinase plasminogen activator system, matrix metalloproteinases, MMP-2, MMP-9, HCCLM3 cells, drug screening
- MeSH terms
- Alginates, Cell Survival, Extracellular Matrix, Gels, Carcinoma, Hepatocellular, Hexuronic Acids, Humans, Liver, Liver Neoplasms, Microspheres, Particle Size, Phosphorylation, Tumor Cells, Cultured, Spheroids, Cellular, Cell Culture Techniques, Tissue Inhibitor of Metalloproteinases, Mitogen-Activated Protein Kinase 1, Glucuronic Acid, Matrix Metalloproteinases, Cell Line, Tumor, Mitogen-Activated Protein Kinase 3, Tissue Scaffolds
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