TABLE 3.
Engineered glioblastoma models.
| Model | Key findings | Refs. |
|---|---|---|
| 2D matrix models | ||
| PA | Spreading, migration and proliferation increases with matrix stiffness, depending on tumour cell subpopulation and patient | 72,74,75,78,179 |
| Silicone rubber | Spreading increases with elastic modulus | 73 |
| Collagen | Matrix biophysical properties affect phenotype | 180,181 |
| HA | CD44 is mechanosensitive; elastic modulus affects miRNA expression | 77,182,183 |
| 3D matrix models | ||
| Collagen | Dimensionality determines drug resistance; Porosity and density affect invasion speed |
181,186 189,190 |
| Collagen-agarose | Cell spreading and motility in collagen requires local matrix stiffening | 187,188 |
| HA | Cell invasion through HA mimics invasion in the brain and is slow relative to invasion in highly porous matrices | 123,183 |
| Matrigel | Stromal cells in 3D matrix affect GBM phenotype | 119,167,16 |
| PEG | MMP degradability enhances cell spreading | 193 |
| PNJ | Scaffolds increase stemness of GSCs | 196 |
| PCL-HA | HA maintains stemness of GSCs | 195 |
| Alginate-chitosan | Scaffolds increase stemness marker expression | 197 |
| HA-collagen | HA upregulates invasion | 207 |
| HA-gelatin | HA upregulates matrix remodelling | 45,208 |
| HA-PEG | Matrix elastic modulus affects ECM deposition | 209 |
| Brain-derived ECM | Cells exhibit brain-like invasion in matrix | 198,199 |
| Models of heterogeneity | ||
| Elastic modulus patterning | Higher modulus increases cell spreading in 2D and 3D | 215,217 |
| Orthogonal parameter patterning | Composition and stiffness have non-linear effects on phenotype | 182,216 |
| Soluble cue gradient | Reduced nutrient and oxygen transport increases secretion of angiogenic factors | 218 |
| Topographical models | ||
| ECM interface | Interface properties drive invasive morphology | 219,220 |
| Open channels | Stiffness and pore size have combined effect on invasion | 179 |
| Electrospun fibres | Linear topographic cues drive rapid invasion | 194,221–226 |
| Encapsulated fibres or channels | Cells transition to rapid invasion when encountering linear topographic cues in 3D matrix | 123,207 |
| Interstitial fluid models | ||
| Flow in Boyden chamber | Interstitial flow drives CXCR4-dependent invasion | 95–97 |
| Multi-parameter microfluidic system | ||
| Pseudopalisade model | Vaso-occlusion drives migration and psuedopalisade formation | 228 |
| PVN models | Stromal-cell crosstalk affects invasive phenotype | 199,229–231 |
| 1. Mini-brain with macrophages | 2. GBM cells recruit and influence macrophage polarization | 3.238 |
| Organoid | ||
| Tumour organoid culture | Tumour organoids maintain heterogeneity and hypoxic gradient | 239 |
| Stem-cell derived tissue | Engineered neural tissue supports brain-like GBM invasion | 241 |
CXCR4, C-X-C chemokine receptor type 4; ECM, extracellular matrix; GBM, glioblastoma; HA, hyaluronic acid; miRNA, microRNA; PA, polyacrylamide; PCL, polycaprolactone; PEG, polyethylene glycol; PNJ, poly(N-isopropylacrylamide-co-Jeffamine M-1000® acrylamide); PVN, perivascular niche; GSC, glioblastoma stem cell.