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International Journal of Bioprinting Microfluidic-assisted 3D bioprinting

4.2. Coupling MST with 3D bioprinting: building 3D ionic crosslinking represents a valid and widespread
constructs solution, enabling to solidify and extrude the bioink using
Spun fibers alone cannot replicate the hierarchical 3D a coagulation bath or coaxial wet-spinning systems.
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architecture found in human tissues, limiting the use of in Recently, a new approach is emerging in the
vitro models to the fabrication of elongated structures such biofabrication panorama, consisting of the creation of
as blood microvessels and kidney proximal tubules. 3D handled platforms to spin cell-laden fibers directly in
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bioprinting has lately come to the fore as a revolutionary the site of interest. 163-166 This innovative solution, which
technology for biofabrication. Contrary to mere MST, the takes the name of in situ bioprinting, has a large number
combination of MST with 3D printing enables the precise of advantages compared to the other methods including
control of the arrangement of fibers into predetermined its printing versatility and ease of use. Moreover, in
3D shapes. This allows for the creation of heterogeneous situ bioprinting minimizes the manipulation of printed
and anisotropic constructs that more closely resemble constructs, avoiding the risk of damage or contamination,
the complexity of the in vivo environment and ultimately and allows the body itself to act as a bioreactor, creating the
impart the desired tissue functionality. optimal conditions for physiological tissue regeneration.

4.2.1. 3D bioprinting 4.2.2. Coaxial wet-spinning 3D bioprinting
Analogous to 3D printing platforms, 3D bioprinters enable Coaxial wet-spinning 3D bioprinting relies on fiber
the deposit of bioinks (material inks comprising living deposition through a coaxial nozzle that is driven in the 3D
cells) to fabricate 3D living constructs. In the context of space thanks to the movement of the 3D printing machine
biofabrication, 3D bioprinting platforms comprise laser- (Figure 6b). Due to the easy and low-cost fabrication,
assisted, 143-146 inkjet, 147-149 and extrusion-based systems to coaxial needles or capillaries can be assembled in a variety
generate viable and functional tissue substitutes. In this of configurations to spin uniform, 162,167 hierarchical (e.g.,
review, we are focusing on MST integration in bioprinting core-shell, spindle-knot), multi-component fibers, or
systems, typically in extrusion-based machines, where combinations of them.
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bioinks are processed into complex filaments before being
extruded. However, it is worth mentioning that Wang et al. In the frame of vascular tissue engineering, hollow
have recently demonstrated the possibility to integrate a fibers can be produced by flowing the crosslinking
microfluidic mixer with a DLP-based fabrication system to solution or a fugitive material (e.g., polyvinyl alcohol
create multi-functional 3D gradients. [PVA], Pluronic F-127) in the core compartment. 169-171
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Gao et al. demonstrated the possibility to use a coaxial
Custom-made 3D bioprinting systems are commonly needle to deposit hollow fibers within a coagulation bath,
realized by combining computerized driving of the nozzle obtaining lattice, cylindrical, and thick cubic structures.
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in the XYZ direction with a pumping apparatus, which can In a further study, the same group built a system to
be either air-, piston-, or screw-driven, to perform robotic create a 3D vessel-like structure by extruding a fiber and
dispensing of biomaterials. The extruded fiber represents wrapping it around a rotating rod. Fibroblasts and
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the building block of the ultimate 3D-printed construct, smooth muscle cells are embedded in the spun fiber, while
and fiber diameter (in the sub-millimetric range) provides endothelial cells are subsequently seeded in the lumen of
the final resolution. A 3D bioprinter can be equipped with the cylinder. In this way, the authors were able to create a
different tools acting as printing heads, which can be either vascular tube that has been ultimately proven to support
simple syringes with a needle, coaxial nozzles made from internal flow. As another example, Pi et al. presented
glass capillaries or metallic needles, microfluidic devices with another promising multi-channel coaxial extrusion system
coaxial nozzles or monolithic PDMS chips (Figure 6, Table 2). harnessed to 3D-print hollow filaments, which recapitulate
In the simplest case, since shear-thinning materials circumferentially multi-layered tubular tissues such as
can retain their shape after extrusion, they can be blood vessels and urethra. This approach also enabled
directly extruded from a syringe and deposited onto a the fabrication of continuous fibers alternating single and
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substrate (Figure 6a). This approach, called DIW, is multi-layered cross-section (Figure 7a). In 2022, Wang
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sometimes coupled with photocuring 151-157 and, owing et al. demonstrated the possibility to bioprint functional
to its simplicity, undoubtedly represents the most widely acellular hollow conduits, recreating the structure of
used biofabrication method. In the case of extremely low- veins and arteries. Specifically, to obtain fibers with
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viscosity biomaterial inks, free-form 3D objects can be internal lumen, the CaCl solution was flown in the core
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printed inside a supporting bath to retain the target shape compartment while a single or two types of materials were
and subsequently crosslinked to enable the removal of the flowed in the sheath compartment. Smooth muscle cells,
construct from the embedding medium. 158-160 Alternatively, either derived from veins or arteries, were seeded on top

Volume 10 Issue 1 (2024) 58 https://doi.org/10.36922/ijb.1404