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International Journal of Bioprinting Bioprinting of β-islet-like constructs
3.2. Vat polymerization printing regarding the viability of cells in millimeter and centimeter
Vat polymerization printing (VPP) includes a group of tissues and the time taken to complete the graft. Still, it
3D-printing processes in which an energy source selectively proves to be excellent in high-density grafts, as clogging
initiates the polymerization and crosslinking of hydrogel is a nonissue, with postprint cell death being the most
materials to form 3D structures . 3D bioprinters usually prominent issue. Besides the time taken by the printer,
[76]
provide the possibility of precise molding of highly viscous shear stress may cause cell damage or phenotype change
cell-containing hydrogels on a 3D printing bed. Then, this (Table 2) [82,83] . The extrusion-based bioprinting approach is
material should be induced to crosslink to create a hard the most commonly used technique to produce functional
texture and thus form the desired object. VPP process pancreatic islet-like tissue for T1D. In addition to other
system uses ultraviolet (UV) radiation, visible light, and emerging tissue engineering technologies, extrusion-
even laser beams to cure material in a prefilled vat . based bioprinters enable core-shell printing by a coaxial
[77]
In stereolithography, regarded as the first 3D printing nozzle and also combine extrusion with blue light or UV
method, which was introduced by Charles W. Hull in curing during and postprinting (Figure 2B and C) .
[84]
1986 , a photoinitiator inducer is used to crosslink Several published studies use extrusion-based techniques
[78]
hydrogel materials . At present, utilizing photoinitiators, to reconstruct pancreatic islet-like tissue (Table 3).
[79]
such as eosin Y and lithium phenyl-2,4,6-trimethyl benzoyl
phosphinate (LAP), is preferred for curing photopolymers 4. Scaffold-based and scaffold-free
in bioprinting because UV radiation can damage the strategies
DNA of cells . The photocurable hydrogels used in this
[80]
system can be polymers activated with acrylic acid, such as Three-dimensional printing using various bioinks has
polyethylene glycol-diacrylate (PEGDA), hyaluronic acid provided an efficient tool for researchers in the field of
[85]
methacrylate (HAMA), and gelatin-methacrylate(GelMA) tissue engineering and regenerative medicine . Bioink
[86]
(Figure 2B and Table 2) . composition is an essential issue in 3D bioprinting .
[77]
Depending on the components, bioinks are classified into
3.3. Material extrusion two main types: (i) scaffold-based bioinks in which cells
Microextrusion printers rely on using heat to extrude a are loaded into hydrogel materials and (ii) scaffold-free
filament onto a print surface, directly creating a 3D figure bioinks in which only cell aggregates or cell strands are
[86]
of thermoplastic with no need for postprinting gelation. eventually formed in the constructs . Whether scaffold-
It is already commonly used in nonbiological 3D printing based or scaffold-free printed grafts have the best result
and is developing in the field of fabrication of hard depends on the type of graft required. One of the main
tissues and porous scaffold design. Unlike jetting-based issues with scaffold-based models is the uneven seeding of
bioprinters, there are no droplets involved in material cells within the scaffold itself, where the scaffold-free model
extrusion printing. Material extrusion bioprinter uses cell- prevails over scaffold-based. In the bioprinting of tissues
[86]
laden hydrogel biomaterials, also known as bioinks, which and organs, the use of scaffold-based bioink is common .
are loaded into the cartridges extruded from the nozzle via
pneumatic or mechanical force in a filamentous form . 4.1. Scaffold-based strategies
[81]
Robotic motors are used to control the location of the In most body tissues, cells require ECM to carry out specific
dispensed filaments, and the size depends on the nozzle activities and even survive. ECM provides structural
[87]
regulating the extrusion and putting the spatial resolution cohesion, mechanical strength, and elasticity of tissues .
between 5 μm and 1 mm, which is far more precise than Scaffolds are 3D networks mimicking the physicochemical
[88]
material jetting printers, allowing for the resolution that properties of the natural environment for cells . They
can produce single-cell deposition or scaffold printing. function as the ECM analogue, keeping cells in place and
Extrusion-based bioprinting prefers higher densities of resisting stress while allowing nutrient diffusion and cell
printing materials as opposed to low densities in jetting- migration. Usually, scaffolds are made from biocompatible
based bioprinting, as low-density materials do not perform and biodegradable materials of biological or synthetic
well under the excessive pressure to extrude filaments . origin. Several prior studies have focused on selecting the
[82]
Owing to the higher density in extrusion-based printing, ideal material for encapsulating pancreatic islets. Scientists
a problem arises in diffusing nutrients and oxygen have concentrated on tailoring macroporous hybrid
to the cells within the matrix. Thus, porous scaffolds, scaffolds of natural and synthetic polymers, which have the
[89]
interconnected channels, and vascular networks have oxygen-generating or vascularization-enhancing ability .
been used to address this problem. The printing speed also OxySit is an in situ oxygen-generating hydrolytically
poses an issue in larger grafts, as the speed is limited to active biomaterial in the form of solid calcium peroxide
[90]
10–50 μm/s speed by current technology, causing an issue encapsulated in polydimethylsiloxane (PDMS) . This
Volume 9 Issue 2 (2023) 262 http://doi.org/10.18063/ijb.v9i2.665

