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International Journal of Bioprinting Fluid mechanics of extrusion bioprinting

Based on the working principle, 3D bioprinting more biomaterials, synergistically enhance biological and
techniques can be classified into extrusion bioprinting, inkjet mechanical properties. 28
printing, acoustic-droplet ejection, electrohydrodynamic For extrusion bioprinting, bioinks should have the
(EHD) jetting, stereolithography, laser-induced forward following properties: (i) the bioink should flow easily
transfer, and laser guidance direct writing. Each of these
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techniques has its respective advantages and disadvantages. through the needle while also retaining its shape after
Among these, extrusion bioprinting is the most extrusion, (ii) the printed filaments should exhibit
commonly used due to its high printing speed, scalability, and maintain good structural integrity and adhesion
and ability to print a wide range of bioink viscosities between the printed layers, and (iii) the bioink should
(30–6 × 10 mPa·s). 9–12 Furthermore, extrusion bioprinting support cell survival and function during and after the
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29,30
is a feasible method to fabricate scaffolds with high cell bioprinting process.
density and anatomical porosity, which is challenging Given that extrusion bioprinting relies on the flow of
for other bioprinting techniques. However, extrusion liquid bioinks before gelation on the printing stage, fluid
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bioprinting has its limitations, notably the difficulty in mechanics is crucial for its success. It explains the process-
obtaining fiber diameters smaller than 100 μm. This fiber induced forces on the cells, printability of bioinks, and
resolution is notably lower compared to those achievable instabilities that can affect the bioprinting process, as
by inkjet and laser-based printers, i.e., 50 and 5 μm, well as the mixing process in multi-material bioprinting
respectively. As a result, extrusion bioprinting has limited techniques. Conversely, hydrogels and polymer melts
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accuracy in cell patterning and organization. 14 reveal viscoelastic and thixotropic behaviors, making their
Hydrogels are frequently employed as support fluid analysis more intricate. Despite the importance of
materials in bioinks due to their advantageous properties fluid mechanics in the bioprinting process, many crucial
for promoting cellular growth. 15–18 They share similarities aspects have not been discussed or documented in previous
with the extracellular matrix (ECM) in terms of high reviews on bioprinting. In this paper, we review the recent
water content, porosity enabling nutrient and gas studies on the extrusion bioprinting process from the fluid
exchange, biocompatibility, and biodegradability, making mechanics viewpoint and discover how fluid mechanics
them appealing for cell therapy applications. 19,20 Natural can affect the outcomes of bioprinting. Dimensionless
hydrogels, such as alginate, gelatin, agarose, chitosan, numbers are powerful, widely used tools in fluid mechanics
collagen, and hyaluronic acid, are commonly utilized in for generalizing test results. They normalize length scales,
synthesizing bioinks. 21–24 Scaffolds biofabricated from time scales, velocities, or forces affecting a physical
natural hydrogels or synthetic bioinks are essential in phenomenon, representing the geometrical, kinematic,
tissue engineering, providing a favorable environment and kinetic similarity of different flow conditions. As such,
and physical support for cell function and interaction. dimensionless parameters, including Reynolds, Weber,
1
Besides, these scaffolds can also serve as delivery vehicles Weissenberg, Elasticity, and Péclet numbers, are used
for growth factors to promote and regulate tissue growth. 25 and presented in various sections, providing generalized
In the bioprinting process, constructs are typically criteria to assess the flow and mixing behavior during the
formed through layer-by-layer deposition of bioink(s). To bioprinting process.
achieve 3D cell-laden scaffolds with good structural fidelity,
the bioink should exhibit appropriate rheological behavior 2. Extrusion bioprinting
and rapid gelation characteristics. Besides, the bioprinting This section reviews and presents the fundamentals of
process should be benign to prevent the damage of cells extrusion bioprinting, including the extrusion driving
during the printing process. While hydrogels with high mechanism, printability, cell viability, and bioink rheology.
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water content provide a suitable environment for cells,
they also exhibit poor mechanical properties. This can be 2.1. Driving mechanisms for extrusion
addressed by utilizing high-concentration hydrogels to An extrusion bioprinter typically comprises a computer-
improve shape fidelity in scaffold bioprinting; however, controlled printing head and a positioning system. During
this may compromise the conditions for cell growth and the printing process, the printing head is controlled to
viability. In contrast, certain synthetic polymers offer move in three directions, while the bioink, stored in a
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favorable mechanical properties, but they often lack syringe that is attached to the printing head, is extruded
biocompatibility. To enhance the mechanical stability out of a tip or needle, depositing on the printing stage
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of cell-laden constructs, researchers utilize both natural to form a 3D structure. The extrusion of bioink requires
hydrogels and synthetic polymers, or composite polymers, energy transfer or mechanical forces, often achieved using
for bioprinting. Hybrid scaffolds, printed from two or a pneumatic system with compressed gas (e.g., air or

Volume 10 Issue 6 (2024) 115 doi: 10.36922/ijb.3973