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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
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