Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research

Table 3

Experimental materials used to study the effect of matrix physical properties on stem cells in vitro.

Polymer; substrates	+ advantages/− disadvantages	Examples	Method to vary elasticity	Reference
Natural polymers
	+ good adhesion capabilities; + mimicking of natural ECM	Collagen-I gel (1 wt.%) and collagen-hyaluronic acid mixture	By the concentration of water soluble carbodiimide (EDC) as a crosslinking agent to produce matrices of 1–10 kPa with pore sizes about 50 μm	[49]
Collagen-based gels		Collagen-I gel (1 wt.%)	By thickness of solution before polymerization: 500 µm for soft, few microns for stiff	[78]
	+ injectable, for brain repair; + biodegradable	Gelatin-hydroxyphenylpropionic acid (Gtn-HPA) hydrogel	By chemical cross-linking by an enzyme-mediated oxidation reaction	[12, 22]
Hyaluronic acid (HA) gel	+ mimicking of natural ECM; − pure HA does not permit cells to adhere; must be coated by cell-adhesion proteins; predominantly elastic, with very low viscous component	Thiol modified HA (HA-S) gel coated with gelatin	By concentration of PEG-diacrylate as a cross linker	[50]
		Hyaluronic acid (HA) 1 wt.%	By the concentration of water soluble carbodiimide (EDC) as a crosslinking agent, pore size 80 μm	[87]
Synthetic polymers
Polyacrylamide (PAA) gel	pure PAA is fully elastic material but can be used to produce viscoelastic gel; + plenty of methods to tune its stiffness without changing porosity or even pore size; − pure PAA do not permit cells to adhere; must be coated by cell-adhesion protein	PAA gel coated with type 1 collagen	By different ratios of acrylamide/bisacrylamide concentrations in a mixture	[55, 62]
		PAA matrices of varying pore sizes but the same stiffness	—//—	[59]
		PAA gels coated with covalently bound tissue-specific ECM proteins (collagen I, collagen IV, laminin, or fibronectin)	By different ratios of acrylamide to cross-linking agents bisacrylamide, ammonium persulfate, and tetramethylethylenediamine (TEMED)	[52, 57]
		Viscoelastic PAA gels in which the loss modulus is varied whilst the storage modulus is kept constant	—//—	[55]
Polyethylene glycol- (PEG-) based gels	+ high elasticity; + cytocompatibility; + ability to be photopolymerized	Polyethylene glycol-(PEG)	By percentage of PEG; polymer in the precursor solution	[10]
		3D thixotropic polyethylene glycol-silica gel (turns liquid under certain stress)	By weight percentage of fumed silica particles incorporated into the gel	[54]
		Polyethylene glycol diacrylate (PEGDA)	By altering the duration of the photopolymerization process	[68]
		Mixture of PEG-dimethacrylate (PEGDMA) and PEG-methacrylate	By different ratios of PEG-dimethacrylate (PEGDMA) and PEG-methacrylate in a mixture	[51, 132]
Polyvinyl alcohol (PVA)	+ stiffness gradient formation	Polyvinyl alcohol (PVA) hydrogel produced by the hydrolysis of polyvinyl acetate	By gradual freezing	[53]
Poly dimethylsiloxane (PDMS)	+ biocompatibility; viscoelastic material; used for micropatterned islands formation	Polydimethylsiloxane (PDMS)	By mixing base and cross-linker at different ratios; by using temperature gradient to create a gradient in the crosslinking density of siloxane	[56, 58, 58, 64, 89]
Electrosrun fibers: micro- or nanofibres drawn from a polymer; solution using; an electric; charge	+ ECM-mimicking nanofiber structure, allowing control over fiber diameter; + allowing achieving high porosities or large pores; + ability to be photopolymerized; + useful to form 3D matrix; + useful to create substrates of different topology	Polyethylene glycol dimethacrylate PEGdma and poly(ethylene oxide) (PEO)	By adjusting the photopolymerization time	[61]
		Poly(ε-caprolactone) (PCL)	By different ratios of solvents	[65]
		Biodegradable polyurethane (PU) synthesized with using poly(ε-caprolactone) (PCL) as the soft segment	By different ratios of solvents (2,2,2-trifluoroethanol and N,N-dimethylacetamide)	[60]