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Cui, et al.
tissue engineering and other biomedical fields. For the of extrusion 3D printing . However, the limitation of this
[12]
extrusion-based printing, the inks in the cylinder can be method is that the amorphous materials do not have the
extruded under pressure through the nozzle and deposited ability to crystallize. Therefore, it is necessary to develop
on a substrate layer by layer. Therefore, the ink not only more extensive mechanical enhancement strategies.
can be extruded smoothly but also can be set quickly In this study, cellulose nanocrystals (CNC), kind
after deposition. The fact that a printable biomaterial of rigid nanoparticles, were introduced to strengthen the
is required to have the properties of shear thinning, amorphous block copolymer hydrogels. CNC is a rod-
fast curing and good biocompatibility presents a huge shaped rigid nanomaterial made of natural polymers,
challenge in broadening extrudable biomaterial inks [2,8] . which has a good biocompatibility and can be stably
Hydrogels are water-swellable 3D crosslinking dispersed into nanoparticles in an aqueous medium [24-27] .
network with adaptable mechanical strength. Therefore, As previously reported [28-30] , the introduction of CNC
under the premise of retaining the original excellent could mechanically enhance the hydrogels. Therefore,
properties of the hydrogel, enhancing its mechanical strength we hope to introduce such rigid nanomaterials as
to meet the needs of 3D printing is one of the focuses in this reinforcing fillers to improve the mechanical strength
field [9,10] . Nevertheless, the diverse and complex gelation and printability of amorphous hydrogels. Thus, triblock
mechanisms of hydrogels are reciprocally restricted copolymers, poly(ε-caprolactone/lactide)-b-poly(ethylene
with technology condition of extrusion-based printing, glycol)-b-poly(ε-caprolactone/lactide) (PCLA-PEG-
thereby restraining the application in 3D bioprinting. PCLA), were chosen for the study. A series of PCLA-
Thus, it is an application prospect to develop more PEG-PCLA copolymers with different molecular weight
extrudable hydrogels with easy gelation mechanism [11,12] . were prepared; subsequently, different amounts of CNC
Temperature-responsive hydrogels are the soft materials were introduced, and the mechanical improvement
that can reversibly transit between gel and sol by regulating effect on the hydrogels was evaluated. It is found that
temperature, which are the ideal printable and extrudable the addition of CNC significantly improved the thermal
materials . Unfortunately, the crosslinking network of stability and mechanical strength of the hydrogels.
[13]
this type of hydrogels is often based on hydrogen bonds Within a certain concentration range, the improvement of
or hydrophilic-hydrophobic interactions. The weaker hydrogel performance was proportional to the increase of
forces lead to poor structural stability and low mechanical CNC concentration. In addition, when a certain amount
strength of the cross-linked networks. Extrusion swelling CNC was added, the sol system that cannot form a gel
and even structural collapse will occur during printing [14-16] . state at room temperature has a significant “liquid-solid
Therefore, the present research focuses on enhancing the transition” phenomenon. More importantly, the CNC-
mechanical strength of the hydrogels while retaining the enhanced hydrogels could form effectively maintained 3D
original excellent properties. structural objects with high resolution and fidelity during
At present, the introduction of carbon-carbon double the printing process, and no extrusion swelling or structural
bonds in the chemical structure of the materials, and collapse was observed. The strategy of introducing rigid
subsequently photo-curing is the main means. Among nanoparticles such as CNC to the mechanically weak
them, methacryloyl gelatin (GelMA) is a representative of hydrogels meets the demand of 3D bioprinting, and is a
this strategy. In this approach, the chemical modification simple and effective way to improve the comprehensive
is easy and convenient. The degree of substitution of performance of the thermal-sensitive hydrogels.
the double bond can be adjusted while the structure of
the gelatin will not change significantly. The printed 2. Materials and methods
GelMA object can be fast photo-crosslinking by adding 2.1. Materials
a photoinitiator. The mechanical strength of the cured
hydrogel is remarkably enhanced [17-20] . However, the CNC (11 wt%) was purchased from Beijing North Tianchen
introduction of photoinitiator and its free radical species Technology Co., Ltd. (Beijing, China). ε-caprolactone
caused by UV irradiation that causes damage to the cells (98%) was received from Shanghai Aladdin Biochemical
affect the cell survival rate [21-23] . We previously reported Technology Co., Ltd. and dehydrated by CaH for more
2
an alternative approach: introducing a crystalline poly(ε- 2 weeks. PEG (M = 6 000, 8 000 and 10 000 Da) was
n
caprolactone) (PCL) block into the molecular structure to purchased from Sigma-Aldrich (98%) and dehydrated by
construct poly(ε-caprolactone)-b-poly(ethylene glycol)- lyophilization. L-lactide (LLA) was synthesized in our
b-poly(ε-caprolactone) triblock copolymer. The results lab and recrystallized from ethyl acetate and dried in a
showed that the crosslinked network of the copolymers vacuum oven at room temperature over 3 days. Stannous
could partially crystalize in water. Compared with the octoate (Sn (Oct) , 95%) and CDCl 99.9%) were also
3 (
2
amorphous control group, it showed significantly improved obtained from Sigma-Aldrich. All other chemicals
strength and thermal stability, which meets the requirements were obtained from Shanghai Chemical Reagent Co.
International Journal of Bioprinting (2021)–Volume 7, Issue 4 113