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Scaffolds produced by combining porogen leaching and emulsion templating
two length-scales: a larger bulk porosity typically in thickness as these treatment methods have limited
the region of 30 – 50 µm which is interconnected by depth penetration into the material .
[30]
smaller (1 – 5 µm) pores [8-18] . As the name suggests, These limitations can be overcome by
polyHIPE scaffolds are initially formulated as an introducing another tier of porosity into the
emulsion. These are typically created by mixing a polyHIPE network in the form of larger (>200 μm)
hydrophobic monomer, crosslinker, initiator, and pores . This creates a multiscale porosity scaffold
[8]
a suitable surfactant to form the continuous phase ideal for bone tissue engineering with pore sizes
of the emulsion, then slowly adding an aqueous over three length-scales: pore interconnects,
internal phase. This creates a water-in-oil (W/O) standard polyHIPE pores, and additional
emulsion where the constant mixing breaks the macropores. Approaches to creating larger pores
water into isolated droplets dispersed throughout inherent in the polyHIPE have focused on creating
the continuous monomer phase. To form a high large water droplets in the initial emulsion. This
internal phase emulsion (HIPE), the internal phase can be done using high temperatures or solvents
volume ratio must exceed 74% of the total emulsion to destabilize the emulsion in a controlled way
as this ensures that droplets form interconnects to cause droplets of water to coalesce into larger
when polymerized. The continuous phase can be ones . However, as these changes affect the
[23]
polymerized using either ultraviolet (UV) light or entire HIPE and larger droplets are formed in lieu
thermal curing; afterward the internal phase drains of smaller ones, this means that a further scale of
away leaving behind a highly porous polyHIPE . porosity is not added. Another limitation to this
[19]
The parameters used during the emulsification approach is the effect on pore interconnectivity.
process directly affect the structure of the final Pore interconnects form during polymerization
polyHIPE material. Physical actions such as the between adjacent water droplets if the film
speed of mixing [20,21] , the rate at which water of continuous phase surrounding the droplets
is added and the emulsion temperature all is sufficiently thin. Below this threshold, the
[23]
[22]
affect internal phase dispersion, geometry, and contraction of the material as it polymerizes
the final porosity as the droplets act as a template causes small interconnecting pores to form ;
[31]
for the continuous phase to polymerize around. hence, monomers that have high shrinkage during
Furthermore, the type and quantity of the emulsion polymerization create more interconnectivity in the
constituents also affect the final architecture, polyHIPE scaffold . Larger water droplets have
[25]
including the internal phase volume , monomer a thicker continuous phase film surrounding them
[24]
type [25,26] , solvent addition , concentration of the which will be more resistant to these contraction
[17]
surfactant (or particles in Pickering emulsions) [21,27] , forces, resulting in fewer interconnects.
initiator solubility , and the concentration of An alternative approach to introduce an
[28]
electrolytes in the aqueous phase . All these additional, larger scale of porosity to the polyHIPEs
[26]
affect porosity and/or pore interconnectivity is by 3D printing the HIPE in additive manufacture.
of the polyHIPE. The commercial success of By building structures from polyHIPE struts that
Alvetex , a polystyrene polyHIPE, shows the do not exceed the inherent depth limitations of
®
suitability of this class of materials for 3D cell traditionally manufactured polyHIPEs, porous
culture . However, these membranes are only scaffolds capable of filling larger defects can be
[29]
200 μm thick as cellular penetration into the bulk produced . This approach results in multiscale,
[8]
material is limited, primarily because of factors hierarchical, and interconnected porous scaffolds
such as diminishing mass transport and nutrient that have superior nutrient and waste transport
availability. Furthermore, with polyHIPE scaffolds while benefiting tissue regeneration. They
created from hydrophobic monomers, surface have smaller (1 – 50 µm) microscale pores
treatments such as plasma etching/coating are that benefit cellular performance and larger
necessary to overcome the inherent hydrophobicity pores (>300 µm) that facilitate ingrowth and
of the material. This reduces maximum scaffold permit large quantities of extracellular matrix

100 International Journal of Bioprinting (2020)–Volume 6, Issue 2