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polymers, and bioactive agents under the control of a theories that involve cell-laden polymer solution
CAD model in a layer-by-layer fashion. It can produce solidification and crosslinking mechanisms have been
bioartificial organs with specialized biomaterials, proposed by Professor Wang .
[66]
complex shapes, and internal microstructures .
[62]
To achieve the ideal functionality and 3.3. Approach of vascular network 3D printing
biocompatibility of the “bioinks,” special characteristic There are two approaches for vascularize network 3D
requirements need to be fulfilled for the generation of printing, direct printing and indirect printing. Direct
vascularized organs. Most critically, biomaterials should printing has fewer requirements in manufactory steps as
show the inherent characteristics for vasculogenesis, it generates the vascular networks in a continuous, layer-
angiogenesis, and biofunction of natural blood vessels. by-layer process. Direct printing can be widely used in
Natural hydrogels, comprised collagen, gelatin, elastic all printing systems with outstanding feasibilities during
fibers, elastic lamellae, and proteoglycan, have been used and after printing. On the contrary, indirect printing
frequently as organ printing “bioinks” . The activity, utilizes a sacrificial template to achieve an advantage in
[63]
proliferation, and differentiation of cells in the “bioinks” geometrical and microfluidic perspectives compared with
are one of the main factors affecting organ functions. direct printing. The accurate of the external structures is
Besides, thin printing filaments of polymers have restricted.
become the mainstream for lowering cell apoptosis due Vascularized organs with blood vessels can be
to the nutrient permeation capabilities. In addition to the effectively generated using a direct approach. Suri et al.
branched vascular networks, a “bioink” should possess fabricated a microchannel incorporated 3D scaffold
the characteristics of biocompatibility, biodegradability, using glycidyl methacrylate hyaluronic acid . The
[67]
and biostability. Therefore, polymers occupy the utilization of pre-patterned substrate within the SLA
preponderance of “bioinks” for their inherent engineering system introduced the partial photopolymerization
properties. of the “bioinks.” Layers were incorporated with the
Natural polymers have many advantages for being process of consecutive deposition-wash-off deposition.
used as “bioinks” for bioartificial organ 3D printing. First, Various microstructures with different internal patterns
they are widely available and can be easily extracted are printable in sandblasted and acid-etched SLA .
[68]
from animals, crustaceans, trees, and microorganisms, Laschke et al. generated PLGA-based scaffolds and
such as bacteria and fungi. Second, natural polymers created angiogenetic vascular networks with the additive
are biodegradable, biocompatible, and chemically/ of growth factors . Gravity is the common cause of the
[69]
physically/enzymatically cross-linkable with different pleated in the microlayer and the micronozzles are easily
biofunctional groups. Third, most of the natural polymers blocked causing an erratic fluid stream. To eliminate
can dissolve in water, the resulting solutions can be easily the obvious issues in the direct horizontal 3D printing
transformed to hydrogels, for accommodating cells with system, Hinton et al. introduced a modified thermoplastic
no harms. Fourth, the biodegraded products of natural extrusion-based 3D printing system . The extra
[70]
polymers can be recycled or discharged by human bodies. syringe pump extrusion system is integrated with gelatin
One limitation of natural polymers for vascularized organ microparticles for 3D printing using cell-laden hydrogels
construction is that the mechanical properties of the as the “bioinks.” The direct printing platform was highly
cell-laden hydrogels are too low to be anti-suture. To functional in generating coronary-like vascular trees and
overcome this shortcoming, synthetic polymers are often other complex curvilinear structures with hydrogels.
employed to improve the biophysical properties of the The indirect printing approach utilizes sacrificial
3D-printed constructs . materials to generate a specific template with the desired
[64]
To generate proper “bioinks” for vascularized geometrical features. The non-sacrificial “bioinks” are
organ 3D printing, biomechanical features of the 3D printed around the sacrificial template. Afterward, the
printable polymers are the primary consideration for the sacrificial template is removed. In the circumstances
application of the vascular networks. Biocompatibility of vascular network generation, some sacrificial
of the polymers can effectively maintain cell viability, templates are effective in the creation of complicated
degradability, as well as promotes cell proliferation and networks simulating in vivo vasculature. For instance,
vascular network formation. As for tissues with abundant microchannels with opening ends were precisely generated
capillary networks, such as liver and kidney, multitubular utilizing the liquefaction temperature difference between
structures are often needed. Therefore, the printing the polydimethylsiloxane substrate and the gelatin
accuracy, setting speed, and crosslinking capability of the mesh . The gelatin mesh with micromodulation is one
[71]
“bioinks” are all needed to be considered . Printability of the commonly used sacrificial materials. In another
[65]
plays a critical role in regulating the fabrication process study, after collagen hydrogel was encapsulated in the
of the vascular networks. A series of organ manufacturing gelatin template and heated up to 37°C, interconnected
International Journal of Bioprinting (2022)–Volume 8, Issue 3 237

