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Recent cell printing systems for tissue engineering

cell-laden bioink enables the production of accurate F127, polyethylene glycol dimethacrylate [60–62] , etc.
3D shapes and can be applied to the regeneration of 4.2 Bioink Viscosity and Crosslink Ability
tissues demanding high mechanical strength because
the enhanced mechanical properties and high cellular One of the important variables in producing bioinks
with the materials above is viscosity. Viscosity is
activity of the structure. Most importantly, a 3D defined by the concentration of the materials, and the
structure like the natural tissue structure can be de- printability and print resolution can be enhanced as the
signed by placing bioink with different cells on each viscosity of the bioink increases. However, it is re-
layer of the structure. However, the cells that con- ported that cell viability can decrease from the severe
tacted the PCL struts showed dramatically low viabil- nozzle wall shear stress generated in a narrow noz-
ity owing to the hot temperature of the melted PCL zle by high pressure, and this is required to print
during printing. This remains an issue to overcome. high-viscosity bioink [63] . In addition, it is known that
In an additional hybrid application, Yeo et al. [22,57] the ability to crosslink effects the strength and stiff-
developed a hybrid fabrication of a hierarchical scaf- ness of the scaffolds and the oxygen and nutrient
fold using an electrospinning method to align fine supply for the cells. However, excessive cross-linking
PCL nano-fibers on the micro-sized PCL struts created can reduce the cell viability and disturb the formation
from a melt-plotting process as shown in (Figure of new tissue [36] . Therefore, it is essential to develop
5c) [56] . Then, they printed alginate-based bioink with a biodynamic bioink with appropriate viscosity and
myoblasts on the electrospun fibers to examine the crosslink-ability that can be printed in a 3D layered
alignment and stretching of the myoblast cells. Using structure with sufficient printing resolution.
this method, they successfully fabricated muscle mi-
metic scaffold with sufficient mechanical properties. 4.3 Applications of Bioink in 3D Cell Printing Tech-
In addition, the myoblasts in the scaffold were well niques
aligned on the nano-fibers as the aspect ratio of The studies of bioink focus on the process conditions
F-actin with aligned fibers was over 2 folds of the as- to control the viscosity and the bioink’s ability to
pect ratio with random fibers or without fibers, which crosslink depending on the compositions of the mate-
indicates the elongation of the cell in one direction. rials. The printability in 3D printing is an important
These results showed that the fabricated scaffold was factor as well as good biocompatibility that promotes
suitable and applicable for the regeneration of muscle and maintains high initial cell viability over 90%, cell
tissues. proliferation, and differentiation. Therefore, investiga-
4. Bioink tions in bi oink composed of different hydrogels
have been actively performed and applied to regene-
4.1 Definition of Bioink rate various cells with 3D cell printing techniques
(Table 3). For laser assisted 3D cell printing and inkjet
In cell printing, hydrogels made of natural and syn- 3D cell printing, fibrin bioink is widely used because
thetic polymer materials are mainly used in the fabri- of its degradability, enhancement of cellular activities,
cation of a 3D cell structure. The bioink is defined as a and, most importantly, high printability by fast-gelling
mixture of hydrogel and live cells and is the most im- and tunable viscosity [64] . In addition, the fibrin bioink
portant requisite for the successful production of an can be easily obtained from blood by purification and
artificial tissue. The bioink requires several characte- provides binding affinities that help initial cell at-
ristics: (1) 3D printability with uniform viscosity, (2) tachment [64,65] . For micro-extrusion based 3D cell
physical and chemical crosslink ability that enables printing, alginate is the most widely used materi-
3D shape maintenance after printing, (3) cyto-com- al because it is inexpensive, and its viscosity can be
patibility that supports favorable cell viability and as- easily controlled [17,44,46] . In addition, it contains excel-
sists cell proliferation and differentiation, and (4) bio- lent biocompatibility, low toxicity, and a stable 3D
degradability after transplantation into a host for the structure by simply mixing with the carboxyl of
emission of decomposed wastes [58,59] . Currently, the L-guluronic acid in a ca lcium ion solution [66,67] . De
most widely used bioink materials in cell printing are spite those advantages, alginate itself lacks bioactive
alginate, collagen, hyaluronic acid, gelatin, pluronic factors inducing cell attachment or activities. There-

36 International Journal of Bioprinting (2017)–Volume 3, Issue 1