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International Journal of Bioprinting Microfluidic-assisted 3D bioprinting

impacts the central stream diameter or the shear stress a hydrolyzed form of collagen; (ii) alginate, derived from
created at the fluid interface. 87 algae; (iii) chitosan, extracted from arthropods’ shells;
A variety of biocompatible methods for crosslinking (iv) silk fibroin, a protein found in silk produced by most
fibers in microchannels have been proposed, falling under insects; and (v) fibrinogen, a component of human blood.
the categories of light-induced, chemical, and physical In certain applications, biomaterial inks are directly
gelation. In the former case, fiber hardening is induced by derived from the ECM collected from the target tissue,
the activation of photosensible species (i.e., photoinitiators) which is ready to host new cells after going through a
either by ultraviolet (UV) light 63,78,88-91 or by UV-visible decellularization process.
radiation. 72,73 Biocompatibility of photoinitiators and light The choice of a correct biomaterial is a crucial element
exposure has been assessed for a wide range of mammalian for a successful outcome of microfluidic spinning. The
cell types and found to have a minimal impact on cell achievement of the multi-faceted characteristics desired
death. 92,93 Nevertheless, to undergo photopolymerization, for the final product 101-103 must be combined with the
biomaterial inks must be functionalized with photosensitive constraints intrinsically imposed by MST. Indeed, to allow
chemical groups (e.g., methacryloyl groups), reducing microfluidic manipulations and extrusion from nozzles,
the range of available materials. In the case of chemical materials need to be in the liquid phase and, right after
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crosslinking, the polymer precursor instantly solidifies the spinning process, must undergo sol-gel transition to
when it comes into contact with crosslinking agents maintain their shape and retain embedded living cells.
such as monomers or enzymes present in the secondary Common biomaterial inks are based on hydrogels which
solution. 75,82,84,94 As an example, fibrinogen harnesses the comprise a solution of high-molecular-weight polymers
mechanism involved in blood clotting to form fibrin gel dissolved in an aqueous solvent. Before crosslinking
when enters into contact with thrombin enzyme. Several provides the final rigidity, the polymer chains can
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mechanisms, instead, are involved in physical crosslinking, slide without constraints relative to each other and the
including solvent exchange, non-solvent-induced phase solvent, depending on their chemistry and conformation
separation, solvent evaporation, and ionic interactions. (e.g., linear vs. branched polymers), conferring the
In the latter case, ionically crosslinkable materials (such required fluidity to the ink. However, in this state, chain
as alginate) hold the ability to rapidly gel in the presence entanglement hinders relative motion under equilibrium;
of ionic species, which intercalate between specific therefore, the material can sustain a certain level of shear
chemical moieties. This method is one of the most popular stress—the so-called yield stress—before flowing. After
approaches in biofabrication contexts due to its great the yield stress is exceeded, the entangled chains start
simplicity, quickness of gelation, and biocompatibility. 96,97 sliding, and the material keeps on deforming under shear,
like a viscous fluid. The faster the material is sheared, the
The paramount advantage of coaxial wet-spinning
methods is the decoupling of printing capability from easier chain sliding occurs as single chains get more and
more elongated. As a result, the apparent viscosity of the
material rheology, allowing the extrusion even of low- ink decreases with the shear rate, defined by a rheological
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viscosity material blends that include a quick-crosslinkable behavior called shear thinning (as opposed to shear
component (e.g., alginate). Moreover, the method can thickening, a response that is usually of no interest in
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envision cell encapsulation as the process is entirely biofabrication contexts).
biocompatible. Other spinning processes, such as melt-
and dry-spinning, are not biocompatible due to the harsh
conditions required (e.g., high temperature, toxic solvents, 3.3. Theoretical model of a biomaterial ink flow
etc.), resulting in the undisputed success of wet-spinning in a capillary
MST-based platforms as novel tools to produce biofibers. The need for microfluidic control and structural features of
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Moreover, compared to other spinning techniques extruded fibers hence raises the issue of fluid biomaterial
employed in the TERM field, such as electrospinning, rheology modeling. The first thing to consider is that
MST offers superior control over fiber characteristics and biomaterial inks are far from being Newtonian fluids.
internal arrangement of compartments. Different from elastic solids, for which a stress σ produces
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a deformation ϵ proportional to the stress itself (σ = Mϵ,
3.2. Biomaterial ink design where M is the elastic modulus), in the simple case of
Biomaterials are designed to simulate the extracellular Newtonian fluids, the shear stress produces a liquid flow,
matrix (ECM) environment in terms of composition, according to the equation σ = ηγ˙. Here, η is the shear
stiffness, and cell adhesiveness. For this reason, naturally- viscosity and γ is the relative deformation (γ = ϵ/L, with
derived components are often the best choice. L being the size of the deformed liquid element). This
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Commonly, the biomaterial inks are made from: (i) gelatin, relation implies that for constant σ, the deformation ϵ is

Volume 10 Issue 1 (2024) 52 https://doi.org/10.36922/ijb.1404