Review Article

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/− disadvantagesExamplesMethod to vary elasticityReference

Natural polymers
+ good adhesion capabilities
+ mimicking of natural ECM
Collagen-I gel (1 wt.%) and collagen-hyaluronic acid mixtureBy 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 gelsCollagen-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) hydrogelBy 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 gelatinBy 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) gelpure 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 collagenBy 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 formationPolyvinyl alcohol (PVA) hydrogel produced by the hydrolysis of polyvinyl acetateBy 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]