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Shuai Wang, Jia Min Lee and Wai Yee Yeong

Thermal reversible hydrogel, such aspluronic and In another study, gellan gum methacrylate (GGMA)
GelMa has been used in bioprinting as a sacrificial was first photocrosslinked to form rigid hydrogel. In
mold [72] . Kolesky et al. printed a vascularized 3D the second step, GelMa was diffused into the GGMA
scaffold by co-printing pluronic F127 and GelMa. and photocrosslinked, thus forming a soft and ductile
Between 4℃ and 22℃, both Pluronic F127 and hydrogel. The resulting double network hydrogel has
GelMaare are in a solid-like state. Pluronic F127 enhanced the mechanical property. It was reported that
flows readily while GelMa remains stiff at tempera- the resultant hydrogel has a potential in load-bearing
tures below 4℃. On the other hand, Pluronic remains tissue regeneration with strength similar to a
solid while GelMa becomes liquid at temperatures cartilage [82] .
above 22℃. Therefore, based on the temperature ma- Photocrosslinkable hydrogel may achieve good
nipulation, 3 distinct processing windows were printing shape fidelity due to fast curing time. How-
created. Pluronic F127 was printed as sacrificial vas- ever, the photopolymerization process requires a bio-
cular networks embedded in GelMa matrix. After compatible photoinitiator that works well with the
photo-crosslinking of GelMa, the vascular network hydrogel to achieve desirable curing depth and rate.
was created by removing Pluronic F127 at tempera- 4.4 Electric Field Responsive Hydrogel
tures below 4℃. Following that, endothelialization of
vascular network can be done by seeding human vein Electric field responsive hydrogels change swelling
endothelial cell (HUVEC) on the remaining GelMa properties in response to the applied electric field.
channel wall. Using this technique, Kolesky et al. This group of materials are usually made of polyelec-
demonstrated the potential to print perfusable vascu- trolytes, therefore, are pH responsive as well. The
latures that mimic natural fine capillaries [73] . main advantage of electric field responsive hydrogels
The main limitation of printing temperature- over other pH responsive gels is the control of swel-
responsive hydrogel lies in the controlling of temper- ling properties by modulating the electric field. Elec-
ature threshold, as well as the need for a fast sol-gel tric field responsive hydrogels can undergo swelling,
transition time. shrinking, or bending depending on the stimuli
factors [83–88] .
4.3 Photocrosslinkable Hydrogel For example, acid sodium salt-modified pluronic

Polymer solution with containing cells can be rapidly hydrogel experience bends in salt solution without
crosslinked by a brief exposure to UV light [74,75] . Dur- contacting with anode or cathode when electric field
[84]
ing the curing process, photoinitiators generate free applied . As shown in Figure 3, when electric field
+
radicals that can initiate the polymerization was applied, Na migrated towards the cathode elec-
process [69,74,76] . The use of proper exposure time, light trode. As a result, hydrogel material facing the cathode
intensity, and photoinitiator allows minimum cell displayed more prominent swelling than the side fac-
damage as well as crosslinking density [77–79] . ing the anode.
For example, a tubular tissue construct was printed Another example is the use of Poly(acrylic acid)
by a two-step photocrosslinking strategy. After com- (PAA) hydrogel microsphere as a drug delivery sys-
[89,90]
bining partially photocrosslinked gelatin methacrylate tem . PAA hydrogel microspheres showed rapid
(GelMA) with hyaluronic acidmethacrylate (HAMA), and sharp shrinkage when electric field was applied,
a gel-like fluid was printed into a defined pattern. A due to electroosmosis and electrophoresis. This con-
second irradiation of the printed base layer formed a trollable change in shape resulted in an “on-off” re-
more solid structure and a tubular construct was lease of encapsulated drug. This material system has
built [80] . been used as an insulin carrier.
Xiao et al. combined photocrosslinkable GelMA There hasn’t been a direct application of electric
with silk fibroin (SF) into an interpenetrating polymer field responsive hydrogel as a bioprintableink, par-
network (IPN). These GelMA–SF IPN hydrogels have tially due to the lack of cell-binding motif in most of
higher Young’s modulus and are resistant to collage- the synthetic polyelectrolytes. Future studies could be
nase digestion. In addition, by varying GelMa and SF done on hybrid hydrogel system with synthetic polye-
ratio, the IPN hydrogels’ structural and biophysical lectrolyte and ECM proteins such as collagen or gela-
properties can be tuned [81] . tin.

International Journal of Bioprinting (2015)–Volume 1, Issue 1 7