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International Journal of Bioprinting Decellularized materials for bioprinting of liver constructs

perspectives of the organ-specific bioink research domain exhibits some drawbacks related to exposure to harmful
are presented. ultraviolet (UV) light.
Although the bioprinting field is still in its infancy,
2. Overview of three-dimensional combination of materiobiology, computer-aided design, and
bioprinting research printing techniques has enabled the successful bioprinting
of various biomimicking constructs [34,45] . Compared to
3D printing relies on preprogrammed digital blueprints or
predetermined model devised by computer-aided design traditional tissue engineering methodologies, bioprinting
data to generate scalable and reproducible 3D-physical techniques offer several advantageous properties that are
[28,37,39,44,46-50]
constructs by sequentially depositing materials of interest not achievable with conventional approaches .
in a classical layer-by-layer format. The possibility of Functionality and maturity of bioprinted constructs
using additive manufacturing in biomedical field kick- are prerequisites. Indeed, these two issues are the main
started a race for the convergence of printing engineering, constraints in the transition of bioprinted tissue products
[51-62]
material chemistry, and cell biology/tissue engineering. from the laboratory to the clinical setting . To
Currently, bioprinting techniques based on extrusion, understand the basic concepts and operating principles of
inkjet, laser, and stereolithography are being extensively printing technologies suitable for bioprinting applications,
[63-69]
explored for the precise construction of bioartificial soft- the readers can refer to more specialized reviews .
to-hard tissue-like structures for drug screening, disease 2.1. Overview of bioink and key requirements
modeling and eventual clinical applications [22,28-33] . The Bioink refers to a printable cocktail of hydrogel
working principles of these techniques are different, and embedded with cells and bioactive molecules that
each approach has its own uniqueness, but they are not provide a 3D microenvironment to support cell growth,
free from the shortcomings that affect the manufacturing proliferation, migration, differentiation, and postprinting
process and bioprinted constructs. The production of viable maturation [70-73] . Bioink not only constrains embedded cells
biostructures emulating natural tissues/organs features and bioactive components to build complex structures but
highly relies on the appropriate choice of bioprinting also provides a hydrous 3D-microenvironment conducive
method and adopted bioink materials. For examples, to the permeation of oxygen, nutrients, and other soluble
inkjet technology is considered suitable for bioprinting metabolites. An ideal cell-laden bioink exhibits excellent
of small constructs to repair tissue defects. However, liquid absorption, wetting and swelling properties
the application of inkjet methods remains limited due for regulating cell infiltration, motility, adhesion, and
to shear and thermal stresses on cells. Furthermore, the remodeling . Hence, finding a cytocompatible ECM
[74]
need for low-viscosity bioink significantly affects the surrogate with appropriate physiochemical and biological
mechanical stiffness, rigidity, and stability of inkjet-printed properties is the basic requirement for the preparation of an
structures. Extrusion bioprinting allows the printing of ideal bioink and cell encapsulation [75-78] . The reinforcement
bioink materials of different viscosities, which opens up of novel materials in the bioink formulation process is
a wider choice of biomaterials for printing the equivalent not only crucial to modulate the rigidity or stiffness of
of larger tissues and organ-like structures. However, this the structures, and to protect the biological performance
affects the process for finer resolution and the phenotype of cells during the printing process but also to ensure the
and behavior of encapsulated cells. Unlike inkjet and functionality of the cells embedded within 3D-bioprinted
extrusion printing, laser-assisted bioprinting technology constructs. Research is still ongoing to design novel
uses energy from a laser source to produce cellular and bioinks using natural, synthetic, or semisynthetic materials
tissue patterns at relatively high resolution. The main (Figure 1). Critical milestones in bioinks design and their
advantage of laser-assisted printing is the better survival formulation are determined by the physiomechanical
rate of cells after printing because no nozzles are required characteristics (viscosity, viscoelasticity, porosity, topology,
and the bioink material does not come in direct contact architectural fidelity, tensile strength, rigidity, and stiffness),
with dispensing or ejection components. However, there biochemical properties (composition, crosslinking, gelation
are several drawbacks, including cost, thermal damage kinetics, biodegradability, degradation rate, insolubility in
to cells, and cytotoxicity from laser and photoinitiators. cell culture medium, and immunological compatibility) of
Stereolithography is another promising bioprinting the target tissues/organs (Figure 2) . The implementation
[79]
method that can produce patterned structures with higher of bioprinting technologies for the successful fabrication of
resolution and precision. Still, its application is limited viable 3D-printed structures and their clinical translations
because it requires only light-curable biomaterials with are directly linked to bioink cytocompatibility, stability,
high physical and chemical properties. Stereolithography and sustainability. Therefore, important determinants
does not use a nozzle, but like laser-based methods, it of bioinks, such as biocompatibility, nonimmunogenic

Volume 9 Issue 3 (2023) 342 https://doi.org/10.18063/ijb.714