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International Journal of Bioprinting                             Review on Hybrid Biomanufacturing Systems



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                                                      [75]
            Figure 4. (A) Multi-head tissue/organ building system (MtoBS) , with permission from Institute of Physics Publishing (publisher). (B) Multi-arm
                        [77]
            bioprinter (MABP) , with permission from PERGAMON (publisher). (C) Bioscaffolder.
            and  even  core-shell  structure  filaments.  Schuurman   which was irradiated with UV light and visible light during
            et al. (2011) used the BioScaffolder to fabricate hybrid   and after printing, respectively . The UV light equipped
                                                                                        [82]
            constructs by alternate deposition of thermoplastic fibers   with RegenHU enabled rapid gelation and gave rise to
            and hydrogels . With this system, mechanical stiffness   long-term mechanical stiffness. This produced cell-laden
                       [80]
            can be tailored by changing fiber spacing, orientation   hydrogel constructs with more open and porous network.
            and/or thickness. The achieved Young’s moduli of printed   Using the 3D Discovery’s layer-by-layer UV curing system,
            constructs are within the same range as those of native   Zhuang et al. (2019) built thick cell-laden constructs with
            tissues  (e.g.,  cartilage:  4.1  MPa;  trachea:  3.33  MPa).   high shape fidelity and mechanical properties suitable
            Moreover, complex anatomically shaped constructs were   for soft tissue engineering applications  (Figure 5B). In
                                                                                              [83]
            fabricated by co-depositing sacrificial components as   addition,  hybrid  scaffold  constructs  were  printed  using
            a temporary support for overhanging geometries and   the pressure-assisted extruder and screw-assisted extruder
            removed after fabrication by immersing the constructs in   in  3D  Discovery.  Visscher  et al.  (2016)  developed  a
            aqueous solutions. The BioScaffolder was utilized since   contraction-free biocompatible PCL/collagen I/III hybrid
            it can build 3D objects by the coordinated motion of   scaffold (Figure 5C) for ear cartilage tissue engineering .
                                                                                                           [84]
            several dispensing heads, which deposit on a stationary   A PCL cage was printed with the screw-assisted extruder,
            platform .                                         and collagen was inserted into the cage using the pressure-
                   [81]
                                                               assisted extruder before the cage printing was completed.
            3.2.2. FBSs                                        The biomechanical results showed that the extracellular
            FBSs are more advanced and complex systems that combine   matrix deposition increased Young’s modulus in the hybrid
            different techniques, such as electrospinning (or alternative   structures.
            electrowriting methods) and post-processing methods,   BioFactory (RegenHU, Switzerland) (Figure  5D) is
            to enable the fabrication of specifically functionalized,   a further iteration of the platform designed to create
            complex, multi-material, multi-scale, and hierarchical   3D organomimetic models for tissue engineering. The
            tissue constructs.                                 system is a versatile and cell-friendly biomanufacturing
              A popular hybrid biomanufacturing system is the 3D   system that conbines biomanufacturing, electrospinning
            Discovery (RegenHU, Switzerland) (Figure  5A), which   and bio stimulation functions in a single unit, allowing
            combines screw-assisted extruder, pneumatic-assisted   for embedded of cells, biomolecules, a range of soft and
            extrusion head, inkjet printing, melt electrospinning writing,   rigid biomaterials in 3D composite constructs to simulate
            and UV light curing. Extrusion-based biomanufacturing   natural environment [85,86] . The control technology at the
            with 3D Discovery has produced 30 wt.% GelAGE 1MM  (allyl:   micro-nano scale is dramatically promoted with various
            SH = 1:3, 0.05 wt.% I 959 or 1/10×10 −3 m  Ru/SPS in PBS),   electrohydrodynamic technologies. A wide range of printing
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            Volume 9 Issue 1 (2023)                        328                      https://doi.org/10.18063/ijb.v9i1.646
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