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International Journal of Bioprinting Nozzle optimization for multi-ink bioprinting

and biomaterials (bioinks) are printed using a 3D printer, material bioprinting. However, the reported single-nozzle
3–6
a process known as 3D bioprinting. This method provides systems used only high-viscosity inks (100–10,000 Pa·s). 20,23
3D structures of cells and biomaterials in specific patterns, Most bioinks are of low viscosity (<10 Pa·s) 24–26 because
presenting a promising approach for constructing artificial high viscosity can damage the cells in the bioink due to
tissues or organs. 7,8 the shear stress during extrusion. The viscosity is crucial
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The main bioprinting methods are extrusion-based, at the interface of multiple liquids, and the sharpness of
vat polymerization-based, and material jetting-based the switching phenomenon within a single nozzle is likely
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bioprinting. 6,9,10 In particular, extrusion-based bioprinting to decrease as ink viscosity decreases. The behavior of
is widely investigated for its simplicity and ability to low-viscosity bioink inside a single nozzle has not been
accommodate various bioinks that maintain high cell thoroughly investigated. Therefore, understanding this
viability. However, despite its advances, challenges behavior is necessary for developing a single-nozzle
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remain in building large, complex structures with high printing system that can efficiently handle multiple types
fidelity due to limited resolution and printing speed. 8,11,12 of bioinks.
For instance, printing an organ-scale structure might In this study, we utilized numerical simulations to
take 2–10 h, potentially decreasing cell viability in the understand the behavior of bioink inside a single nozzle
bioink. Additionally, current 3D bioprinting technology and propose a design capable of switching multiple inks
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produces simple structures using a single bioink with with high resolution. Numerical simulation, a tool for
limited functionality. Therefore, a multi-ink printing analyzing fluid behaviors in the bioengineering field, 29–31
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technique capable of constructing large-scale structures is employed to facilitate the development of a novel
using multiple bioinks with high resolution and rapid single nozzle that can efficiently switch between bioinks
printing speed is essential. Considerable research has been of different viscosities, at lower cost and in shorter time
directed toward these challenges 11,15 ; nonetheless, further than that of experimental approaches. A dual-inlet system,
exploration is necessary. which is a single-nozzle printing system, was considered
Generally, a multi-nozzle printing system, where for the analysis as a simple example. We introduced a
multiple inks are extruded from separate nozzles, is new physical quantity called switching efficiency (Se) to
analyze bioink behavior and examined the effects of the
employed for multi-ink printing. 16,17 While this system nozzle’s conjunction area design and bioink viscosity on
allows for the fabrication of complex 3D structures the efficiency of bioink switching. Sodium alginate (SA)
composed of multiple inks by increasing the number aqueous solutions, known for their biocompatibility,
of nozzles, switching inks can be time-consuming due shear-thinning properties, and mechanical properties,
to the need to calibrate each nozzle separately. For were utilized as model bioinks. 24,32,33 Our findings suggest
example, Brunel et al. reported 3D printing a structure that switching efficiency depends on both the design of
that mimicked the human heart with cardiomyocytes and the conjunction area and the viscosity of the bioink. In
endothelial cells using a multi-nozzle printing system and particular, viscosity greatly affected Se, indicating the need
a support bath. This 3D-printed structure had a high for a single design to switch different viscous bioinks. Based
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resemblance to the actual human heart, but it had a volume on these results, we proposed nozzles capable of switching
of less than 1 cm . To scale up this construct, the process between bioinks of different viscosities with high efficiency,
3
of changing materials should be improved. Moreover, the and line structures of different viscous SA inks were printed
complexity of the 3D printer increases with the number of using the nozzles to evaluate their performance. To the
nozzles in multi-nozzle systems. Thus, multi-ink printing best of our knowledge, this is the first reported study using
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technology is required, which can rapidly switch inks with both numerical and experimental approaches to enhance
high resolution and speed in extrusion-based bioprinting. the single nozzle in multi-ink bioprinting. 34–36
In contrast to multi-nozzle systems, single-nozzle
systems, which extrude multiple inks from a single 2. Materials and methods
nozzle, offer rapid switching capabilities. Skylar-Scott et 2.1. Materials
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al. achieved high-resolution printing of silicon ink using Tyramine hydrochloride and water-soluble carbodiimide
a single nozzle that can switch materials within 1 s at a (WSCD) were sourced from Combi-Blocks (CA, USA)
resolution of 0.5 mm, enabling the printing of complex and Peptide Institute (Osaka, Japan), respectively.
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and large (>50 cm ) structures. Similarly, Cameron et al. N-Hydroxysuccinimide (NHS) and sodium persulfate
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reported the use of a single nozzle for printing with starch (SPS) were purchased from Fujifilm Wako Pure Chemical
ink at a resolution of 5 mm. These systems would be Industries (Osaka, Japan). Ru(bpy) ·Cl ·6H O was
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2
2
3
desirable for achieving high speed and resolution in multi- procured from Sigma-Aldrich (St. Louis, MO, USA).
Volume 10 Issue 5 (2024) 153 doi: 10.36922/ijb.4091