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International Journal of Bioprinting Fluid mechanics of extrusion bioprinting

The stability of coaxial streams exiting the dispensing The combination of microfluidic bioprinting with
nozzle is crucial for successful bioprinting. Upon exiting coaxial techniques allows for the fabrication of core–
the nozzle, biomaterials in both the core and sheath layers shell fibers with exceptional accuracy and control. 144,145,150
may experience swelling if the flow exhibits a Weissenberg Microfluidic devices typically benefit from integrated
number greater than the Wi , i.e., corresponding to the control systems that facilitate on-the-fly switching between
cr
onset of extrude swell. Typically, the core flow contains different biomaterial sources and precise regulation of
a low-viscosity bioink or Newtonian crosslinker with flow rates in the channels. Multiple channels enable quick
minimal swelling. However, if the viscoelastic biomaterial transitions between different materials or even cell-laden
in the sheath layer exhibits a high swelling ratio, it can exert and cell-free filaments. 151
pressure on the core flow, potentially causing instabilities While various approaches to microfluidic bioprinting
and breakup of the core into droplets. To mitigate this, have been developed, there is still potential for improving
most coaxial nozzles are designed with the core needle the efficiency of these processes. A major limitation of
slightly longer than the sheath needle to protect the core microfluidic bioprinting is the high shear stress experienced
flow from the swelling effects of the sheath flow. by cells within the microchannels, which can reduce cell

4.1.3. Single-nozzle multi-material heads viability. One solution to this issue involves creating a
Continuous single-nozzle multi-material (SNMM) sheath flow that surrounds the laminar core flow, acting
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bioprinting is a technique that involves dispensing different as a protective barrier for the cells. Although Lee et al. 153
biomaterials sequentially through a single nozzle. The managed to mitigate cell stress in a microfluidic head by
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SNMM bioprinting head may include a selector valve to implementing a sheath flow to protect and center the cells
control the printing of different bioinks. Considering within the flow, their system did not include micromixers.
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the internal volume of the head and the diffusion rate of Furthermore, their study focused on glioblastoma
bioinks, any change in the flow rate of precursors results multiforme (GBM) tumor cells, which are less sensitive to
in a delay in the composition of fiber, proportional to the stress compared to normal cells. 148,154
internal volume of the head. Therefore, there is always Y-chips can be utilized in microfluidic printing to
a “transition distance” during which the composition facilitate the feeding of multiple materials into the printing
gradually shifts from one composition to another. 139–141 head. 148,155 By employing two syringe pumps, bioinks can
The drawback of single-nozzle methods is that they be sequentially pushed through two channels connected
cannot print various biomaterials simultaneously. This can to a single nozzle. This allows for the fabrication of
be addressed by using a bundle of capillary nozzles inside constructs with distinct transitions between different
the printing head. Liu et al. developed a multi-material constituent materials.
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bioprinting platform featuring a bundle of capillaries Figure 10 illustrates various microfluidic chip designs
inside a single nozzle, each connected to different bioink used for multi-material bioprinting. 152,156 Design A features
reservoirs. This setup allows for the continuous deposition a Y-passage that enables the simultaneous deposition of
of multiple bioinks from a single nozzle, enabling the two bioinks. Design B features a switching system that
creation of heterogeneous 3D constructs using various alternates between two bioinks, allowing for alternating
biomaterials and cell types. multi-material bioprinting. Design C uses grooved-wall
4.1.4. Microfluidic multi-material heads with micromixers to blend two or more bioinks together. Design
separated streams of biomaterials D has a serpentine micromixer, suitable for fluid–fluid and
Microfluidic devices offer precise control over minute fluid–solid (cell) mixing. Design E employs a sheath flow
volumes of fluids (10 –10 −18 L) through intricately to protect cells within the core flow by positioning them at
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designed microchannels with diameters in the tens of the center, where shear stress is lower. Design F, known as
micrometers. This level of control allows for superior the flow-focusing design, regulates the fiber diameter by
management of fluids in both spatial and temporal adjusting the ratio between the core and sheath flow rates.
domains. Microfluidics-assisted 3D bioprinting utilizes In designs E and F, coaxial flow of viscoelastic
microchannels to guide the flow of bioink, enabling precise biomaterials or Newtonian crosslinkers is employed. Unlike
control over flow, switching, component mixing, 146,147 coaxial nozzles, microfluidic sheath flow or flow-focusing
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and print resolution. The integration of a multi-nozzle chips do not utilize coaxial needles; instead, the core and
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system in a microfluidic head allows for separate extrusion sheath flow are regulated by balancing the effective forces.
paths for each material, which are then combined after The elastic behavior of viscoelastic biomaterials can lead
exiting independent orifices to form desired structures, to complex behaviors inside the flow-focusing microfluidic
such as multi-layer constructs. 149 chip. In coaxial flow, inertial, viscous, capillary, and elastic

Volume 10 Issue 6 (2024) 133 doi: 10.36922/ijb.3973