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3D Bioprinted Organoids
Organoid construction and bioprinting have become extent that subsequent in vitro and in vivo cultures are
research hotspots in the scientific community, and they less effective. In addition, the nozzles are prone to wear
can facilitate the development of truly artificial organs and clogging during inkjet bioprinting, and cells may
in the future, signifying a substantial step forward in the also suffer thermal or mechanical damage, limiting the
field of regenerative medicine. widespread use of inkjet-based bioprinting technologies.

2. Technologies of organoid bioprinting 2.2. Laser‑assisted bioprinting

3D printing is also known as a layer-by-layer stacking, Laser-assisted bioprinting utilizes laser direct-write and
[14]
additive manufacturing method, and the printing laser-induced transfer technologies . A focused laser
technology associated with cell printing is known as 3D pulse is used to generate high-pressure bubbles on the
bioprinting. According to different molding principles ribbon absorption layer, and the suspended bioink is
and printing materials, existing bioprinting methods pushed onto the receiving substrate and then cross-linked.
can be classified into extrusion bioprinting (pneumatic, Compared with other printing techniques, non-nozzle
piston, and spiral), inkjet bioprinting (temperature control printing methods, such as laser-assisted bioprinting,
and piezoelectric), laser-assisted bioprinting, and photo- can avoid direct contact between the inkjet and bioink,
curing bioprinting. Biological 3D printing techniques use thereby preventing the cell/biomaterial from clogging the
[15]
biomaterials, cells, and/or cytokines as bio-inks to build nozzle and mechanical damage to the cell . Thus, laser-
human tissues and organs. However, to date, no biological assisted bioprinting allows the printing of highly viscous
printing technology can produce synthetic tissues of all biomaterials as well as printing with a high cell density.
sizes and complexities. The aforementioned four primary The constructed organoids exhibit high cellular activity,
biological printing techniques pose certain advantages, high cell density, and improved functionality. The use of
disadvantages, and limitations (Table 1). laser-based bioprinting to prepare 3D patterns for spinal
cord repair with axon-like extensions and high cellular
[16]
2.1. Inkjet‑based bioprinting activity has been reported . Moreover, laser-assisted
bioprinting has been used to deposit human umbilical vein
The inkjet-based bioprinting method was the first endothelial cells (HUVECs) onto the surface of biopaper
bioprinting method used to print cells . It is a contactless using a simple crossover technique; these cells were
[9]
printing process based on traditional inkjet printing differentiated and stretched into a network of vascularized
technology, which uses piezoelectric or thermal driving tissues . However, laser-assisted bioprinting pose several
[17]
nozzles to form a series of liquid droplets according to a shortcomings. First, laser-assisted bioprinting devices are
predetermined 3D structure of biological ink (a mixture difficult to commercialize because the cost is relatively
of hydrogels and cells). Inkjet-based bioprinting has high, the control of the laser printing system is complex,
the advantages of high cell activity, fast printing and there are limited hydrogel materials suitable for laser-
speed, higher resolution, and low cost [10,11] . In addition, assisted bioprinting. Second, the printing efficiency is low,
inkjet-based bioprinting can use multiple nozzles and each layer of ink is coated repeatedly. In addition,
simultaneously, enabling the simultaneous printing of uniformity cannot be guaranteed, and the process is time-
different bioactive materials, cells, or cytokines. Using consuming and laborious. This makes it difficult to apply
inkjet-based bioprinting technology, scientists have to complex structure printing. Moreover, the side effects
made significant progress in drawing the patterns of of laser exposure on cells are not fully understood, which
molecules, cells, and organs. Researchers have reported limits the use of this technology.
the use of inkjet-based bioprinting and fibroblasts to
design curved, vascular-like suspension structures 2.3. Extrusion‑based bioprinting
without scaffolds [12] . A method of applying high- Extrusion bioprinting is currently the most widely used
throughput inkjet printing to control cell attachment bioprinting strategy that uses air pressure or mechanical
and proliferation through precise, automated deposition stress to control the extrusion of bioink through a
of collagen was also reported [13] . However, due to the nozzle. It can print high-viscosity biomaterials and high-
low driving pressure, inkjet biological printing cannot density cell suspensions . Its greatest advantage is
[18]
print high-viscosity materials or high-concentrations of that it features a wide range of printable biocompatible
cells. Therefore, it is often difficult to fabricate complex materials, covering biomaterials with viscosities
biomimetic tissues or organoids with high cell density extending from 30 to 6×10 mPa/s, particularly hydrogels
7
using the inkjet bioprinting method. Low-viscosity with shear diminishing, and fast cross-linking properties.
biomaterials can reduce the mechanical properties In contrast to the aforementioned two techniques, the
of bioprinted structures but fail to provide a normal biomaterial or cell suspension is squeezed by continuous
or similar physiological environment for cells to the squeezing pressure to form uninterrupted deposits of

20 International Journal of Bioprinting (2021)–Volume 7, Issue 3