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Gelatine methacrylamide-based hydrogels: An alternative three-dimensional cancer cell culture system
Abstract
Modern cancer research requires physiological, three-dimensional (3-D) cell culture platforms, wherein the physical and chemical characteristics of the extracellular matrix (ECM) can be modified. In this study, gelatine methacrylamide (GelMA)-based hydrogels were characterized and established as in vitro and in vivo spheroid-based models for ovarian cancer, reflecting the advanced disease stage of patients, with accumulation of multicellular spheroids in the tumour fluid (ascites). Polymer concentration (2.5-7% w/v) strongly influenced hydrogel stiffness (0.5±0.2kPa to 9.0±1.8kPa) but had little effect on solute diffusion. The diffusion coefficient of 70kDa fluorescein isothiocyanate (FITC)-labelled dextran in 7% GelMA-based hydrogels was only 2.3 times slower compared to water. Hydrogels of medium concentration (5% w/v GelMA) and stiffness (3.4kPa) allowed spheroid formation and high proliferation and metabolic rates. The inhibition of matrix metalloproteinases and consequently ECM degradability reduced spheroid formation and proliferation rates. The incorporation of the ECM components laminin-411 and hyaluronic acid further stimulated spheroid growth within GelMA-based hydrogels. The feasibility of pre-cultured GelMA-based hydrogels as spheroid carriers within an ovarian cancer animal model was proven and led to tumour development and metastasis. These tumours were sensitive to treatment with the anti-cancer drug paclitaxel, but not the integrin antagonist ATN-161. While paclitaxel and its combination with ATN-161 resulted in a treatment response of 33-37.8%, ATN-161 alone had no effect on tumour growth and peritoneal spread. The semi-synthetic biomaterial GelMA combines relevant natural cues with tunable properties, providing an alternative, bioengineered 3-D cancer cell culture in in vitro and in vivo model systems.
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“Addition of Laminin-411 and hyaluronic acid to GelMA hydrogels of 3.4 kPa stiffness enabled ovarian cancer spheroid formation, proliferation and chemoresistance to paclitaxel (Kaemmerer et al., 2014).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Kaemmerer et al., 2014
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Metadata
- Authors
- Kaemmerer, E., Melchels, F. P. W., Holzapfel, B. M., Meckel, T., Hutmacher, D. W., & Loessner, D.
- Affiliations
- Queensland University of Technology (AU)
- Technische Universität Darmstadt (DE)
- Corresponding author
- Loessner, Daniela
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 10
- Issue
- 6
- Pages
- 2551-2562
- ISSN
- 1742-7061 (ISSN-L)
- OpenAlex
- W2091262660
- Cited by
- 219
- References
- 75
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 17 · 2023: 24 · 2022: 26 · 2021: 18 · 2020: 15 · 2019: 24 · 2018: 15 · 2017: 18 · 2016: 19 · 2015: 13 · 2014: 5
- FWCI
- 8.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Biomaterialia (publishedVersion)
- PubMed (publishedVersion)
- Griffith Research Online (submittedVersion)
- Funders
- Australian Research Council
- the Cancer Council Queensland (PIOF-GA-2010-272286, HO 5068/1-1)
- Cells and Tissue Domain Collaborative Research Development
- Institute of Health and Biomedical Innovation
- Queensland University of Technology, Australia
- Marie Curie Fellowship
- German Research Foundation
- Topics
- Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- hydrogels, ovarian cancer, tumor spheroids, ascites, hydrogel stiffness, solute diffusion, extracellular matrix, matrix metalloproteinases, laminin-411, hyaluronic acid, paclitaxel, integrin antagonists, peritoneal carcinomatosis, biomaterials
- MeSH terms
- Acrylamides, Cell Division, Cells, Cultured, Extracellular Matrix, Gelatin, Humans, Hydrogels, Matrix Metalloproteinases, Cell Line, Tumor
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