Peptide-protein Coassembling Matrices as a Biomimetic 3D Model of Ovarian Cancer
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Bioengineered three-dimensional (3D) matrices expand our experimental repertoire to study tumor growth and progression in a biologically relevant, yet controlled, manner. Here, we used peptide amphiphiles (PAs) to coassemble with and organize extracellular matrix (ECM) proteins producing tunable 3D models of the tumor microenvironment. The matrix was designed to mimic physical and biomolecular features of tumors present in patients. We included specific epitopes, PA nanofibers, and ECM macromolecules for the 3D culture of human ovarian cancer, endothelial, and mesenchymal stem cells. The multicellular constructs supported the formation of tumor spheroids with extensive F-actin networks surrounding the spheroids, enabling cell-cell communication, and comparative cell-matrix interactions and encapsulation response to those observed in Matrigel. We conducted a proof-of-concept study with clinically used chemotherapeutics to validate the functionality of the multicellular constructs. Our study demonstrates that peptide-protein coassembling matrices serve as a defined model of the multicellular tumor microenvironment of primary ovarian tumors.
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Tumor spheroids grown in peptide amphiphile-based hydrogels with elastin mimetics, fibronectin, keratin, RGDS and GHK motifs were comparable in morphology, viability and drug response compared to those grown in GelMA and Matrigel.
“Tumor spheroids grown in this hydrogel were comparable in morphology, viability and drug response compared to those grown in GelMA and Matrigel.”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Hedegaard et al., 2020
In 3D multicellular spheroid cultures, addition of fibroblasts, mesenchymal stem cells, or endothelial cells enhances spheroid size, chemoresistance and a stem-like phenotype compared to 3D monocultures.
“In 3D multicellular spheroid cultures, addition of fibroblasts, mesenchymal stem cells, or endothelial cells have been shown to enhance spheroid size, chemoresistance and a stem-like phenotype compared to 3D monocultures (Hedegaard et al., 2020; Tofani et al., 2021).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Hedegaard et al., 2020
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A Comparison of the Mechanical Properties of ECM Components and Synthetic Self‐Assembling Peptides
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Peptide Amphiphile Hydrogels Based on Homoternary Cucurbit[8]uril Host-Guest Complexes
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Novel Ex Vivo Models of Epithelial Ovarian Cancer: The Future of Biomarker and Therapeutic Research
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- Authors
- Hedegaard, C. L., Redondo-Gómez, C., Tan, B. Y., Ng, K. W., Loessner, D., & Mata, A.
- Affiliations
- Queen Mary University of London (GB)
- School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, E1 4NS London, UK.
- Nanyang Technological University (SG)
- Harvard University (US)
- Venue
- Science Advances
- Published
- 2020-10-02
- Volume
- 6
- Issue
- 40
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC7852381
- OpenAlex
- W3091301386
- Cited by
- 76
- References
- 53
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 12 · 2023: 18 · 2022: 10 · 2021: 18 · 2020: 2
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Science Advances (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (publishedVersion, cc-by-nc)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by-nc)
- Monash University Research Portal (Monash University) (submittedVersion, other-oa)
- DR-NTU (Nanyang Technological University) (submittedVersion, cc-by-nc)
- Funders
- ERC Starting Grant (STROFUNSCAFF)
- Program for Innovation and Human Capital from the Ministry of Science, Technology, and Telecommunications of the Government of Costa Rica (MICITT-PINN-PED-014-2015-2)
- UKRMP2 Smart Materials Hub
- Topics
- Physical Sciences › Materials Science › Biomaterials › Supramolecular Self-Assembly in Materials
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- peptide amphiphiles, ovarian cancer, tumor microenvironment, 3D tumor models, extracellular matrix proteins, nanofibers, tumor spheroids, F-actin network, cell-matrix interactions, endothelial cells, mesenchymal stem cells, chemotherapy response, Matrigel
- MeSH terms
- Extracellular Matrix, Humans, Ovarian Neoplasms, Peptides, Biomimetics, Cell Line, Tumor, Tumor Microenvironment
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