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3D Printing and Vascularized Organ Construction
Based on the working principles, 3D printing materials include photopolymers and waxes. By changing
technologies can been divided into several classes: (i) the content of “inks,” cells and polymers can also be
Extrusion-based 3D printing; (ii) inkjet-based 3D printing; patterned into desired shapes . Until present, most of
[56]
(iii) selective laser sintering (SLS); (iv) fused deposition the inkjet-based 3D printers are used for printing tissue
modeling (FDM); and (v) stereolithography apparatuses engineering scaffolds for cell seeding. Limited by the
(SLAs). At present, only extrusion-based 3D printing soft hardware systems of the commercially available
techniques have been widely used for vascularized organ 3D printers, inkjet printheads with multiple nozzles can
construction [41-43] . hardly be updated to increase the printing complexity and
construct size.
(1) Extrusion-based 3D printing There are many limitations for the inkjet-based 3D
Extrusion-based 3D printing is an automatic fluid printing technologies to be used for vascularized organ
dispensing system, in which polymeric materials are construction. These limitations include low polymer
selectively dispensed through one or more nozzles viscosity (ideally below 10 centipoise), low cell density
or orifices. Different form FDM, the extrusion-based (<10 million cells/mL), and low structural heights
extrusion processes do not involve any heating procedures (<10 million cells/mL) . To provide a higher polymer
[57]
except for special circumstances. Polymer solutions concentration or cell density, crosslinking agents are
or hydrogels with or without cells, growth factors, and often used, resulting in some drawbacks, such as blocking
other bioactive agents can be extruded through nozzles the nozzles and changing the material properties [58,59] .
by pneumatic pressure or physical force (i.e., a piston or
screw) in a controllable manner . The printing system (3) Laser-assisted printing technology
[44]
generates continuous filaments under the control of CAD The technological base of laser navigated 3D printing is
models. At present, this kind of 3D printing is capable laser-induced interaction. It adopts a specific “Ribbon,”
to deposit multiple living cells along with biocompatible which is composed of metal (i.e., gold or titanium), a
polymers with very high cell densities. The solidification laser energy absorption layer, and “ink” at the bottom.
of polymer solutions or hydrosols is achieved through The metal layer was evaporated by laser to induce the
a series of physical and/or chemical procedures, such formation of “bioink” droplets and deposited on the
as sol-gel transformation (i.e., physical crosslinking), collecting substrate. Compared with other 3D printing
polymerization, chemical crosslinking, and enzymatic technologies, this technique is relatively effective in
reaction, before, during, or after 3D printing [45-47] . arranging single cells, including human adipose-derived
The main objective of extrusion-based organ 3D stem cells (ASCs) and ECs, thus, it may offer some
printing technologies is to print cell-laden hydrogels along advantages in the construction of capillaries .
[60]
with other biomaterials in layers using CAD models.
Recent advances in the development of the multi-nozzle (4) SLA
3D printers have significantly enhanced their applications
in producing large scale-up vascularized organs, such as In the process of 3D printing, the commonly used
the skin, liver, heart, lung, and pancreas [48-51] . materials for SLA are polylactic acid, polyhexyl acetate,
The advantages of extrusion-based 3D printing in protein, and polysaccharide. This technique is often
vascularized organ construction include high cell densities, used for producing tissue engineering scaffolds. The
large scale-up structures, and extremely sophisticate scaffolds generated with laser energy, even though are not
compositions. A large number of biomaterials, including mechanically robust, provide precise control of resolution.
cells, growth factors, and other bioactive agents, can Compared with the above-mentioned inkjet-based 3D
be simultaneously deposited with polymeric solutions printing, the microscale laser tip is advanced in printing
or hydrogels. With the increase of extrusion nozzles, a accuracy. However, the limitation of this technique in
variety of heterogeneous constructs with multiple polymer vascularized organ construction is that polymers have
and cell types can be constructed. Many researchers have to be photopolymerizable to generate solidified layers in
addressed the effects of extrusion process parameters, the reservoir. Living cells cannot be 3D-printed directly.
such as speed of 3D dispensing, pressure, temperature, Besides, the microstructures can be easily distorted or
nozzle size, viscosity, and shear thinning of polymeric shrunk when they are excessively exposed to the laser
[61]
solutions or hydrogels, on cell viabilities [52-55] . energy .
(2) Inkjet-based 3D printing 3.2. Biochemistry characteristics of the
Inkjet-based 3D printing is a non-contact AM technique, “bioinks”
adapted from industrial 2D printers, in which droplets Compared with the traditional industrial manufacture,
of building materials are selectively deposited. Example 3D printing can precisely arrange living cells, biological

236 International Journal of Bioprinting (2022)–Volume 8, Issue 3