Table 1 |.

Biomaterials for modelling the tumour microenvironment

Biomaterial	Model	Advantages	Disadvantages	Refs
Synthetic material
Polydimethylsiloxane (PDMS)	2D micropatterns	Flexible substrate with patterns promoting cancer cell alignment	Uncertain viscoelastic mechanics and protein attachment	37,148
	Microchannels and microfluidics	• Directed cell migration in channels • Cell confinement • Confined fluid flow for controlled application of shear stress to cells	• Curing ratios often create materials that are less flexible • Static substrate	23,114
Polyethylene glycol diacrylate (PEGDA)	3D culture	• Wide stiffness range • Direct conjugation of many types of adhesive ligands • Can be used to identify tumour-specific stiffness	–	51
Polyethylene glycol (PEG)	3D culture	• Wide stiffness range • Direct conjugation of many types of adhesive ligands or degradable linkers • Inert and biocompatible	Backbone is not degradable	39,149,150
Poly(lactide-co-glycolide) acid (PLGA)	3D culture	• Porous scaffold • Biocompatible • Biodegradable	Methyl side groups increase hydrophobicity	151,152
	Implantable material	Recruitment and capture of metastatic cells	Degradation prior to cell capture	93
Poly(ε-caprolactone) (PCL)	Implantable material	Recruitment and capture of metastatic and immune cells	Degradation prior to cell capture	92
Polyacrylamide	Substrate gradients	• Sequential polymerization to create spatial patterns • Indication of metastatic cell ‘memory’ • Small well polymerization for high-throughput drug screens	Substrate stiffness does not change with time	153–155
	Used with Matrigel overlay for 3D culture	• Wide stiffness range • Conjugation of individual or multiple ligands resulting in nonlinear cell responses	• Cytotoxic prior to polymerization, preventing cell encapsulation • Difficult to measure forces in 3D	3,30,40,45
	Elastic 2D substrate	Measurement of traction forces in cancer cells	• Cytotoxic prior to polymerization, preventing cell encapsulation • Difficult to measure forces in 3D	42
Synthetic-natural hybrid materials
Polyethylene glycol-heparin	3D culture	• Direct conjugation of adhesive ligands • Enzymatically degradable	Limited degradation control	38
Methacrylated hyaluronic acid (MeHA)	3D culture	• Direct conjugation of adhesive ligands • Enzymatically degradable • Temporal gradients through sequential crosslinking	• Radical polymerization limits in vivo application • Can induce DNA damage • Modifications can reduce bioactivity	44,54,55
Natural materials
Matrigel	3D culture	• Established fibrillar model system • Temperature-based polymerization • Easy encapsulation methods • Growth factor-reduced version • 3D organization of acinar structures	• Batch-to-batch variation • Difficult to independently modulate parameters • Tumour-derived (inductive composition) • Temperature sensitive	8,9,11,30
Alginate	3D culture	• Stiffness can be modulated independently of architecture • Time-dependent stiffening with calcium crosslinking • Enables mammary epithelial cells to polarize before EMT	Calcium-dependent covalent bonds	56,156
Type I collagen	3D culture	• Fibrillar • Adhesion of multiple cell types • Facilitates cell invasion • Shows same radiation damage as tumours	• Transglutaminases and oxidases can crosslink with limited range Harsh organics are more common crosslinkers with a wider range • Limited stiffness range of ~1–1,000 Pa	23,35,69,157
	Matrigel-impregnated	Migration is biphasic and directly dependent on concentration	• Pore size changes with Matrigel concentration • Limited ligand presentation	31,32
	Agarose-impregnated	• Stiffness can be modulated independently of ligand density • Restricted invasion of glioma cells	Pore size changes with agarose concentration	63

EMT, epithelial-to-mesenchymal transition.