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International Journal of Bioprinting Review on Hybrid Biomanufacturing Systems

A B

C

Figure 2. Categories of hybrid biomanufacturing systems, including (A) basic multi-head biomanufacturing systems (BMBSs), (B) semi-hybrid multi-head
biomanufacturing systems (SMBSs), and (C) fully-hybrid biomanufacturing systems (FBSs).

with different viscosities, and thus multiple biomaterials, stromal cell types to aid in the in vitro modeling of cancer
cell types or bioactive factors can be deposited within the in three dimensions . With this system, they produced
[61]
same structure, which opens the route for multi-material multi-cell-type tissues and demonstrated that these
and multi-functional scaffold fabrication. Key systems are bioprinted tissues can mimic aspects of in vivo neoplastic
reviewed here. tissues.
NovoGen MMX 3D Bioprinter (Organovo, San By replacing the pressure-assisted head with screw-
TM
Diego, USA) (Figure 3A) is the first commercial extrusion- driven piston actuated extruders, a multi-nozzle low-
based 3D printing system applied in the bioengineering temperature deposition and manufacturing (M-LDM)
[59]
field. This machine was first created by Norotte et al. . The system (Figure 3B) was developed by Liu et al. (2008)
system comprises two dispensing pumps with nozzles (i.e., to fabricate scaffolds with heterogeneous materials and
micropipe) and contains temperature-controlled heating gradient hierarchical porous structures to coordinate
[62]
and cooling modes. This system ensures reproducibility biological properties , such as adhesion, proliferation,
of bioprinted tissues and cell-loaded scaffolds through and differentiation of various cells in both time and
high-precision controlling of the composition of tissue space dimensions. M-LDM system can process various
and the geometry; for example, small-diameter vascular materials, such as PLGA, PLGA-TCP, collagen, chitosan,
[63]
reconstruction (outside diameter: 0.9 – 2.5 mm) has and gelatin .
[59]
been performed using this system . About 5% Gelatin Kim et al. (2009) increased the number of dispensing
methacryloyl (GelMA) hydrogel cylinders have also heads and developed a similar multi-head deposition
been printed by this system to induce ontogenesis for system (MHDS) (Figure 3C) based on pressure-
vascularized bone tissue regeneration . Langer et al. assisted extrusion , and able to process a wide range
[60]
[64]
(2019) used the NovoGen MMX 3D bioprinter to print of biomaterials, such as PCL, PLGA, and various
scaffold-free tumor tissues with cancerous cells and several types of hydrogels (hydroxyapatite [HA], gelatin, and

Volume 9 Issue 1 (2023) 325 https://doi.org/10.18063/ijb.v9i1.646