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International Journal of Bioprinting Extrusion-based biomaterial inks
of extrusion bioprinting is extruded filament; therefore, to the inks printed for liquid support bath bioprinting.
according to the type of filaments, these extrusion The third case is to use fugitive or sacrifice inks (e.g.,
strategies can be classified into single-nozzle bioprinting, gelatin and Pluronic) as the core ink, then the shell inks
co-axial bioprinting, and multi-nozzle bioprinting. can be partially crosslinked pregels or self-support printed
biomaterials that can hold out the structure shape. If the
5.1. Single-nozzle bioprinting core and shell of co-axial nozzle were two phases of water
Micro-extrusion single-nozzle/multi-material bioprinting, and oil, the printing technique would help to fabricate
additional configurations of multi-material bioprinting and uniform microbeads, such as structural color beads used
continuous chaotic bioprinting are all defined as single- for fluorescence detection [183] .
nozzle bioprinting. Only one filament is extruded from a
single nozzle at the same time, and the composition and 5.3. Multi-nozzle bioprinting
combination of multi-materials could vary. Specifically, Multi-nozzle extrusion-based bioprinting is a powerful
in self-supporting bioprinting, biomaterial ink is directly tool to manufacture vascularized organs with hierarchical
printed in the air without structural support materials. internal/external structures for biomimicing multiple
The biomaterial inks for self-supporting bioprinting have physiological functions in vitro, such as bioartificial
excellent viscoelastic properties and mechanical properties lungs and heart. It can also customize the 3D-printed
sufficient to support the printed structure, thus compositing bio-constructs with gradient material constituents by
with rheological additives or structural auxiliary materials controlling the combination of multiple nozzles and
is essential. It is difficult to self-supporting bioprint corresponding biomaterials inks. The nozzles can be
bioactive materials alone, unless they have been chemically divided into two categories of hot melt nozzle and extrusion
modified and pre-gelled. nozzle. The printing strategy can be selected as multi-
extrusion nozzle, or the combination of hot melt nozzle
Embedding bioprinting needs a rapid gelation profile and extrusion nozzle. The principles of multi-extrusion
after free deposition of the filament into a liquid or nozzle in the selection of biomaterial inks are similar to
gelatinous coagulation support bath. For the liquid support that of single-nozzle bioprinting. For the second strategy,
bath, the liquid is usually a solution containing Ca , and the thermoplastic polymers in the form of wires are hot-
2+
the biomaterial inks are generally alginate-based inks melted and deposited into fibers to form scaffolds. Then,
or other hydrogels gelled through cations crosslinking, biomaterial inks are printed onto the scaffolds, resulting in
like gellan gum-based inks and carrageenan-based inks. hybrid constructs. The biomaterial inks can be extended
For the gel support bath, the biomaterial ink can be for different hydrogels and their crosslinking agents to
selected as any compatible materials with extrusion-based demonstrate the feasibility of this versatile multi-nozzle
bioprinting, the gels in the support bath should have shear- bioprinting method.
shinning viscosity behavior and thixotropic behavior to
fulfill the self-supporting bioprinting requirements. More 6. Outlook
importantly, the gels in the support bath can be easily
removed to ensure stability of printing structure and Extrusion-based bioprinting has been successfully used
convenience of post-processing. So far, the use of gelled to construct a variety of in vitro tissue and organ models,
gelatin , gelled agarose [155] , and nanoclay [182] as the gels in which are applied to the fields of drug screening, tissue
[5]
the support bath have been reported. engineering, and regenerative medicine. There are still
some deficiencies and defects that warrant continuous
5.2. Co-axial bioprinting improvement, especially the biomaterial inks, which
The bioprinter corresponding to co-axial bioprinting is represent the most important limitation. Biomaterial
equipped with a coaxial nozzle performing continuous inks contain a wide range of printable biomaterials with
infusion with internal and external flows. The main purpose different properties and functions. Nevertheless, their
of co-axial bioprinting is usually aimed at printing hollow viscoelasticity and gel crosslinking mechanism mainly
fiber directly in one step to fabricate blood vessels or other affect printing performance of the ideal design structures.
tubular structures. One scenario is that the core of the Generally, the excellent printability and high shape fidelity
nozzle provides internal flow with ordinary fluid and non- can be achieved through different printing strategies.
curing molding after printing, then the shell inks must be However, bioactivity and mechanical properties are limited
self-supporting bioprinted with large mechanical strength. by the biomaterial ink itself. Therefore, in the future, the
Otherwise, the shell structure may collapse, resulting in the extrudable biomaterial inks should be developed with
failure to form hollow fibers. The other case is that the core good bioactivity and suitable mechanical property in
of the nozzle provides internal flow with a cation solution, regard to organ specificity, tissue elasticity, and construct
then the shell biomaterial inks are exactly corresponding microporosity, as shown in Figure 8.
Volume 9 Issue 2 (2023) 16 https://doi.org/10.18063/ijb.v9i2.649

