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Solvent-based extrusion 3D printing
these approaches are compatible with the printing of phenotype. They described the dependence of the
relatively high viscosity inks. However, screw-driven bioprinting accuracy on the hydrogel concentration;
based 3D printing is not suitable for the printing of optimization of the ink concentration enable the
cell-laden inks since the shear stress generated on the fabrication of a heart valve shape that matches
blade may cause cell damage [23,24] . the original design. Wüst et al. evaluated
[31]
There is a wide variability among different tissues a combination of alginate and gelatin with
and organs in terms of their material composition and various amounts of hydroxyapatite (HA); human
mechanical properties [25-27] . As such, functionalization mesenchymal stem cells (hMSCs) mixed into the
of 3D scaffolds is dependent on material and mechanical hydrogel/HA inks survived the printing process.
parameters and should be tailored according to these The in vitro results show high cell viability, with
parameters as appropriate. For the development of an 85% cell viability rate after 3 days. The elastic
such scaffolds with SBE 3D printing, several factors modulus of the alginate-gelatin composite discs
should be considered (summarized in Figure 1D). increased with the HA concentration. However, the
These include (a) biomaterial selection for the ink, ink became more viscous as the HA concentration
(b) investigation of the ink rheological behavior, was increased; as such, it is difficult to print
(c) printing process parameters, and (d) assessment HA-containing inks. They indicated that control
of printed scaffold regarding structure, mechanical of the tip temperature affected the viscosity of the
properties, degradation, and biocompatibility. bioink; increasing the temperature can convert the

3 Ink biomaterials for SBE 3D printing in TE ink to liquid form, eliminating the clogging issues
at the dispenser tips.
3.1 Ink materials with cells for SBE 3D printing Notably, more viscous inks require larger
pressures for extrusion from the nozzle; as such,
Biomaterials used in scaffold fabrication are mixed cells in the bioinks are exposed to process-induced
with solvents to create the liquid feedstock for forces (i.e., shear stress). The deformation of the
SBE 3D printing. Table 1 summarizes the use of cell membrane can occur if the applied force is
SBE 3D printing with or without living cells for too high. As such, the shear stress is a key factor
TE. Biomaterials used with living cells in scaffold that needs to be evaluated during bioprinting.
fabrication should not only provide an appropriate Blaeser et al. developed a fluid dynamics model
[32]
environment for cell survival but also should be and performed in vitro experiments to understand
compatible with the printing process. The formulated shear stress at the nozzle site. The results show
biomaterial solution is often called a bioink and the that the generated shear stress is affected by the
processing approach is referred as bioprinting. The hydrogel ink viscosity, extrusion pressure, and
most commonly used biomaterials for bioprinting
are hydrogels (either natural or synthetic hydrogels); nozzle dimensions. Mouse fibroblasts can exhibit
these biomaterials can provide mild aqueous cell viability of 96% if exposed to shear stress of
environment to the cells during the printing process. <5 KPa; viability is decreased to 90% and 75%
The hydrogels used in SBE 3D printing with cells for the shear stress of 5–10 kPa and more than
includes alginate, hyaluronic acid, collagen, gelatin, 10 KPa, respectively.
and silk [12,17,28-30] . 3.2 Ink materials without cells for SBE 3D
Duan et al. formulated hydrogel inks with printing
[12]
hyaluronic acid and gelatin; they incorporated
human aortic valve interstitial cells (HAVICs) The cells do not need to be placed within the
within these inks for 3D bioprinting of heart valve inks. The printed scaffolds can serve as a support
conduits. An increase in the gelatin concentration structure to facilitate tissue regeneration on
resulted in a lower ink stiffness and a higher the inherent recovery properties of the tissue.
viscosity; these parameters facilitated cell spreading Direct ink writing (DIW) is a common applied
and maintenance of a better HAVIC fibroblastic method for printing inks that do not contain

30 International Journal of Bioprinting (2020)–Volume 6, Issue 1