Tissue engineering has produced innovative tools for cancer research. 3D cancer models based on molecularly designed biomaterials aim to harness the dimensionality and biomechanical and biochemical properties of tumour tissues. However, to date, despite the critical role that the extracellular matrix plays in cancer, only a minority of 3D cancer models are built on biomaterial-based matrices. Major reasons for avoiding this critical design feature are the difficulty in recreating the inherent complexity of the tumour microenvironment and the limited availability of practical analytical and validation techniques. Recent advances emerging at the interface of supramolecular chemistry, materials science and tumour biology are generating new approaches to overcome these boundaries and enable the design of physiologically relevant 3D models. Here, we discuss how these 3D systems are applied to deconstruct and engineer the tumour microenvironment, opening opportunities to model primary tumours, metastasis and responses to anticancer treatment.
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This work was supported by the Medical Research Council (UK Regenerative Medicine Platform Acellular Smart Materials – 3D Architecture, MR/R015651/1) to A.M. and the European Research Council under the European Union’s Horizon 2020 Research and Innovation Program (grant agreement number 864253) to D.L.
The authors declare no competing interests.
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Replica of the properties or elements of natural tissues or systems.
Decellularized tissues that preserve the structural and molecular integrity of the organ-specific native extracellular matrix.
Short peptide sequences in biomaterials that present insoluble adhesion ligands and proteolytically degradable motifs and enable binding or release of soluble factors.
- Desmoplastic tumour stroma
Deposition of a dense and crosslinked extracellular matrix resulting in a fibrotic tumour tissue.
- Epithelial-to-mesenchymal transition
When cells become more motile, migratory and invasive through the loss of epithelial features and the gain of mesenchymal ones.
- Fluid shear stress
Force created by the fluid flow parallel to a surface of a material or tissue.
Water-swollen polymer network.
- Interstitial flow
Movement of fluid that is transported through the extracellular matrix.
- Metabolic vulnerabilities
Abnormal metabolism of cancer cells targeted by anticancer therapies.
Self-organizing and self-renewing clusters of cells derived from tissue fragments or stem cells that mimic the functionality and behaviour of tissues.
- Personalized medicines
Therapies designed for a specific patient based on its genetic or individual signature.
3D structure with defined geometry and mechanical properties.
Cell aggregates or clusters that resemble some features of tissues.
Resistance of a material, or tissue, to deformation and alteration of its original shape when a force is applied.
Formation of a tumour whereby normal cells transform into cancer cells following a disrupted differentiation.
- Tumour microenvironment
Dynamic network of malignant and non-malignant cells, extracellular and cell-secreted elements and soluble factors that promote tumour development, growth and metastasis.
A time-dependent mechanical property of materials or tissues that exhibit viscous and elastic responses when forces are applied, causing temporary or permanent deformation, respectively.
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Curvello, R., Kast, V., Ordóñez-Morán, P. et al. Biomaterial-based platforms for tumour tissue engineering. Nat Rev Mater 8, 314–330 (2023). https://doi.org/10.1038/s41578-023-00535-3