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Jang T-S, et al.

86% of viability at day 7 after 3D culturing. Xu et al. of chondrocytes. Hong et al. developed 3D printed
fabricated a composite extracellular matrix by printing PEG/alginate hydrogel composite with stretchiness and
[72]
alginate/gelatin hydrogels with incorporating fibrin toughness . Fabricated hydrogel composites had higher
which is a natural scaffold material [75] . Fibrin acted as fracture energy than the value of cartilage and high cell
an important component to regulate self-organization viability after 7 days of culturing. The toughness of
and differentiation of adipose derived stromal cell. This this hydrogel composite is attributed to the reversibly
printed hydrogel composite functions as an extracellular crosslinked calcium ions dissipating the mechanical
matrix that can offer an environment for cell growth and a energy and the covalently crosslinked PEG chains
platform for drug delivery in soft tissue engineering. The contributing to high elasticity.
gellan gum, a versatile gelling agent, was introduced as Another method to tailor the mechanical strength is
compounding materials in 3D plotting method by Akkineni to co-print hydrogel with a stiffer polymer. Hyaluronic
[76]
et al. They mixed high concentration of alginate and 2–3 wt acid, the main ECM component of cartilarge, with photi-
% of gellan gum. The addition of gellan gum prevents rapid reactive glycidyl methacrylate was printed as a porous
[79]
swelling and thus improves the shape fidelity of printed scaffold by direct ink writing technique . The stiffness
scaffolds. Moreover, human mesenchymal stem cells on of scaffold increased as the contents of functionalized
alginate/gellan gum composites displayed higher degree of glycidyl methacrylate increased. When implanted
cytocompatibility compared with pure alginate. The study in a porcine mandibular model, it showed good cell
explained that the improved initial cell attachment was compatibility and enhanced tissue growth. Bakarich et
related to the mechanical properties of hydrogels; stem cells al. blended alginate/poly(acrylamide) with acrylated
preferred stiffer gels. Many researchers have highlighted urethane UV-curable adhesive (Emax 904) to fabricate
that the cytocompatibility of gels is highly dependent on the biomimetic hydrogel composites [70] . They adjusted the
mechanical properties of the hydrogel matrix. ratio of components by controlling the rates at which two
In attempts to enhance the mechanical properties of materials stored in two separate syringes are dispensed
hydrogel, two-component hydrogels consisting of a into a single mixing nozzle (Figure 4A). As the volume
thermoresponsive polymer mixed with PEG or HAc content of Emax 904 increased, the tensile strength and
were printed by 3D plotting . Starting materials were elastic modulus also increased and this trend was in
[77]
crosslinked by chemoselective reaction and extruded accordance with the rule of mixtures theory. Finally, they
hydrogels showed mechanically stable hydrogels with incorporated varying gradients into the printed scaffold
a storage modulus of 9 kPa after 3 h. The hydrogel to mimic living tissue such as tendon which links soft
composite containing HAc exhibited high cell viability muscles to hard bone (Figure 4B).

Figure 4. (A) The extrusion rate of Emax 904 as a function of the length and image of extruded gradient gel stained with red and blue
dye. (B) Application of gradient gel which mimics the human tendon-muscle-tendon system in the place of pronator teres. (reproduced
with permission from [70]. Copyright 2017, Elsevier Ltd)．
International Journal of Bioprinting (2018)–Volume 4, Issue 1 11