Skip to main content

Table 2 Methods of production of scaffolds and their advantages and disadvantages

From: Three-dimensional in vitro culture models in oncology research

Method of production

Description of the mechanism

Advantages (+)/Disadvantages (−)

References

Lyophilisation/freeze-drying

Polymers are solubilized in solvent, before being subjected to gelation sublimation of solid polymers (gel or foam) followed by freeze drying under vacuum

 + High porosity and pore interconnectivity

– Small pore size

− Irregular porosity

− Time consuming process (days)

− Residual solvent that may be harmful to cells

− High energy-consuming

[142, 143]

SCPL

Insoluble salt particles are added to a solution of polymers solubilized in solvent. After solvent evaporation, a composite of polymers embedded with salt particles is obtained. Repeated washing of the composite with water allows the salt elimination and then the formation of a porous scaffold

 + Simple

 + Reproducible

 + No specific instrument required

− Limited interconnectivity

− Time consuming process (days)

− Residual solvents that may induce cell damages

[144]

Gas foaming

Can be done chemically by: i) producing hydrophobic gas bubbles in liquid solution of polymers; ii) physically by subjecting a solid polymer to a high pressure gas that can dissolve into it and expands when the pressure is reduced, thus producing cavities when the bubbles collapse. It can be associated with SCPL

 + High porosity

 + Controlled pore size

 + Solvent-free

− Limited interconnectivity

[145,146,147]

TIPS

Relies on the change in thermal energy to transform a homogeneous mixture of polymer and solvent into a multiple-phase system, composed of a polymer-rich phase (solvent-poor phase) and a polymer-poor phase (solvent rich phase). The solution is quenched below the freezing point of the solvent, and the solvent is removed by freeze-drying

 + Easily implementable

 + High interconnectivity

 + Easy modulation of pore size and structure

− Time consuming process (days)

− Residual solvents may induce cell damages

− High energy-consuming

[148, 149]

Electrospinning

A charged liquid with a voltage high enough to counteract surface tension will stretch and erupt into a jet. It will solidify into a fibre when projected on a collector

+ High porosity

 + High interconnectivity

+ Low cost

 + Most soluble polymers can be used

 + Mimic the fibrillar structure of ECM

− Complex generation of 3D structure

− Residual solvents that may induce cell damages

− Small pores that lead to poor cell infiltration and distribution

− Low mechanical strength

[150, 151]

Self-assembly

Spontaneous assembling of monomers into supramolecular nanostructures after exposure to pH or temperature modifications or enzymatic treatment

 + Different types of structure can be generated depending on the synthesis conditions

 + Easy to functionalize with various molecules

 + Less toxic because does not require cross-linker reagents

+ Low cost and rapid syntehesis

− Difficult to control size of the self-assembled nanostructure

− May be unstable under liquid conditions

[152, 153]

Rapid prototyping

Describes a group of manufacturing processes (e.g. stereolitography, 3D printing, selective laser sintering) that enables fabrication of scaffold layer by layer with precise spatial organization from a computer aided design (CAD)

+ High control on pore size, porosity, and interconnectivity

+ Good resolution

 + Good reproducibility

− Expensive

− Time-consuming (creation of the design)

− Potential wasting of polymers

− Potential cytotoxicity of the polymers used

[154]

  1. SCPL solvent-casting and particulate-leaching, TIPS thermally induced phase separation