Page 62 - IJB-2-2

Osteosarcoma growth on trabecular bone mimicking structures manufactured via laser direct write

Introduction long process of thermal curing or with increase in

P increased the versatility of PolyHIPE systems, and
[2,4,10,12]
. This approach has potentially
temperature
olyHIPEs are a class of materials where poros-
ity is introduced using a phase separated mix-
there is a growing interest in the use of photocurable
ture by a process often termed as emulsion
templating, in which the continuous phase of high monomers for their production [4,8,11–16] . PolyHIPEs
have been commercialised for use as 3D environments
internal phase emulsions (HIPE) is polymerised. The for cell culture including the development of more
PolyHIPE structure shows promise for 3D cell culture, complex tissue models. In these applications it was
as the porosity may be tailored to produce different reported that the 3D structure encourages the forma-
structures that have the potential to modify in vitro tion of a more physiologically correct tissue structure,
[1]
cell response . For example, the production of larger and the microporosity may facilitate mass transfer
voids can be achieved through controlled coalescence when used in combination with a bioreactor [17] . De-
of the HIPE before polymerisation by rupturing of the spite the benefits of a 3D PolyHIPE scaffold, only
[2]
barrier film by increasing the original emulsion simple shapes are available and mass transfer is rela-
temperature or through the addition of organic addi- tively limited. For example, the internal pore size in
[1]
tives . Typically surface area ranging between 3– commercial systems such as Alvetex (Reinnervate
−1
2
20 m ∙g may be achieved and increased further by Ltd.) generally has a narrow pore size distribution of
replacing a proportion of the continuous monomer 36 to 40 μm .
[1]
phase with non-polymerisable solvents [2,3] . Since the emergence of additive manufacturing, the
Generally, PolyHIPEs are created via thermal po- production of scaffolds with more complex shapes,
lymerisation of the continuous phase which can take e.g., in a specific bioreactor or to engineer an ad-
[4]
up to 24 hours . The most widely used monomers in vanced tissue construct, has been a rich research field,
PolyHIPE chemistry are styrene and its derivatives, and currently different technologies have been re-
and often the crosslinker divinylbenzene, due to their ported for production of biomaterial scaffolds with
hydrophobic properties [1,2,5,6] . Nevertheless, there are complex or custom shapes and hierarchical porosity.
reports of PolyHIPE preparations with acrylate-based For example, additive manufacturing can be used in
monomers such as 2-ethylhexyl acrylate (EHA), iso- combination with electrospinning to produce 3D por-
bornyl acrylate (IBOA) and butyl acrylate (BA) [1,5,6] . ous structures for tissue engineering [18,19] . Additionally,
The addition of EHA increases the elasticity of the indirect additive manufacturing, where a 3D structure
polymer matrix and its hydrophobic properties lowers of a sacrificial material is printed and subsequently a
the interfacial tension between the two phases which porogen-containing material is cast in the voids. The
[7]
results in a lower void diameter . Producing Poly- material is washed to remove both the sacrificial scaf-
HIPE blends of EHA [4,8] , typically with IBOA, pro- fold and the porogen. This method has been demon-
vides a route to control the mechanical properties. strated to produce both vili-shaped surface relief pat-
These materials are water immiscible and offer ade- terns and 3D woodpile-structured with internal poros-
quate rigidity to support cell proliferation which can ity [20,21] . The use of a sacrificial scaffold has also been
[9]
be improved by the inclusion of acrylic acid . How- used in conjunction with electrospinning to produce
ever, they have a non-degradable aliphatic carbon microporous electrospun mats with internal channels
backbone that limits their applications to in vitro use. to introduce a prototype vascular network in these
Photopolymerisation of acrylates to create PolyHIPEs scaffolds [22,23] .
was first reported in 2006 [10] via photo-initiators [11] . A Recent studies reported on the use of layer-by-layer
study by Pierre et al. employed EHA and IBOA mo- stereolithography for selectively photocuring Poly-
nomers with trimethylolpropane triacrylate (TMPTA) HIPE emulsions to fabricate customised structures
crosslinker and Span 80 as surfactant, showing the with both random microporosity and controlled ma-
effect of the monomer choice (EHA or IBOA) on the croporosity [11,13,24] . In this process, the templated
elastic properties of the monolith as well as employing emulsion is used as the resin for the direct write
photoinitiated polymerisation as a curing method [10] . process. The advantage of this process (i) to the indi-
Photoinitiated polymerisation reduces the cure time to rect additive manufacturing process is that the scaffold
seconds, which means that less stable emulsions can is written directly in the porous material, with no need
be cured which might otherwise destabilise during the of building sacrificial materials, and (ii) to additive

68 International Journal of Bioprinting (2016)–Volume 2, Issue 2