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3D Printing and Vascularized Organ Construction

Figure 4. 3D printing of human hearts. Republished with permission of American Association for the Advancement of Science, from
3D bioprinting of collagen to rebuild components of the human heart, Lee A, Hudson AR, Shiwarski DJ, et al., Vol. 365 No. 6452, 2019;
permission conveyed through Copyright Clearance Center, Inc.

metabolic regulation. 3D bioprinting of livers is one of the or dimethyl sulfoxide), have been explored for bioartificial
research hotspots with relatively rapid progression. The organ, especially liver, manufacturing (Figure 7) . The
[94]
first liver pertinent 3D printing technology was reported viscosity of the gelatin-based “bioinks” depends largely
in 2005 in which alginate was used as an additive in on the polymer concentration, molecular weight, and
gelatin-based cell-laden “bioinks” (Figure 6) [87-89] . This cell density. A series of two-step stabilization strategies,
is also the first scale-up larger hepatic tissue construction containing both the thermosensitive physical and ionic
report using extrusion-based RP techniques and cell- chemical crosslinks, for the 3D-printed constructs have
laden hydrogels. With the instruction of CAD models, been exploited. The chemical crosslinking methods include
a brand new era for fully automatic manufacturing glutaraldehyde for gelatin, CaCl for alginate, sodium
2
of bioartificial organs has begun. The RP techniques tripolyphosphate for chitosan, and thrombin for fibrinogen.
together with the resulted living constructs have been Ten years later, this classical RP principles, the hydrogel
later used widely in many biomedical fields, such as solidifications, the “bioink” formulations, and the polymer
controlled cell transplantation, high-throughput drug crosslinking strategies have been extensively adapted by
screening, customized organ restoration, pathological many other groups [95-99] .
mechanism analysis, and long-term bioartificial tissue/ A critical limitation of the 3D-printed cell-laden
organ cryopreservation [90-93] . Thus, it is a fundamental hydrogels for organ manufacturing is the notorious weak
breakthrough in large scale-up organ 3D printing. mechanical properties of the products without anti-suture
In 2009, a double-nozzle/syringe RP technique was and anti-stress functions. A practicable solution is to
created at Professor Wang’s laboratory. Since then, various integrate mechanical strong enough synthetic polymers
gelatin-based composite “bioinks,” such as gelatin/alginate, into the 3D constructs. However, most synthetic
gelatin/fibrin, gelatin/chitosan, gelatin/hyaluronate, and polymers, such as PLGA and polyurethane (PU), do
gelatin/alginate/fibrin, gelatin/alginate/dextron (glaycerol not have sol-gel transition (or phase transformation,

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