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Cited by 219Hydrogels: synthesis, properties, applications3D Printing in Biomedical ResearchCellular Mechanics and Interactions

The DOI matches its Crossref record; 74 of the 75 references it cites were found in a registry or an index.

Gelatine methacrylamide-based hydrogels: An alternative three-dimensional cancer cell culture system

Kaemmerer, Elke, Melchels, Ferry P.W., Holzapfel, Boris M., Meckel, Tobias, Hutmacher, Dietmar W., Loessner, Daniela·2014·Acta Biomaterialia
DOI 10.1016/j.actbio.2014.02.035
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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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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
ORCID
Venue
Acta Biomaterialia
Publisher
Elsevier BV
Published
2014-06
Volume
10
Issue
6
Pages
2551-2562
ISSN
1742-7061 (ISSN-L)
DOI
10.1016/j.actbio.2014.02.035
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
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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