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International Journal of Bioprinting Decellularized materials for bioprinting of liver constructs

studies. Efficient implementation of bioprinting technology of cellular processes essential for cell growth, tissue
for GMP-compliant biomanufacturing of clinical-grade repair, regeneration, and homeostasis through embedded
tissue/organ substitutes suitable for transplantation physical, chemical, and biological cues. Typically, chemical,
will require a multitude of technological and bioink biological, physical, or combative methods are used for
material-related research advancements. The fundamental decellularization. Although experimental procedures for
limitations in achieving complex, implantable, clinical- decellularizing nearly all tissues in the body have been well
grade bioprinted structures include poor resolution, studied, there is still no consensus on the optimal protocol
dimensions, speed, accuracy, and precision. To produce to use for each tissue/organ of various species. This is
biomimetic constructs with accurate geometric and because each tissue has different characteristics in terms of
compositional attributes, bioink must be printed at a source, donor age, size of tissue/organ, abundance of ECM
reasonable resolution ideally comparable to the average contents, morphological appearance, anatomical location,
size of human body cells (10–20 μm). Identification of cytoarchitecture, and cellular density. Therefore, when
functionally graded biomaterials in the formulation of performing decellularization treatments, it is essential to
bioink is another limiting factor in bioprinting research recognize that one protocol may not yield effective results
and mandatory regulatory approvals. for all tissue types [136-149] .

Despite many efforts in bioink formulation, the design The common procedure for preparing bioink using
and development of tissue/organ-specific bioinks (with liver decellularized bioink is to solubilize the extracted
minimum sol–gel transition and crosslinking duration and purified ECM crystals, enzymatically (pepsin)
without nozzle clogging) suitable for specific bioprinting digest them, and adjust the pH and ion concentration.
of functionally graded bioconstructs are still limited. Although decellularized liver materials have remarkable
To fabricate industrial-scale bioprinted structures for biophysicochemical properties, their low mechanical
implantation or repair/replacement of damaged/diseased strength makes it difficult to maintain stability, stiffness,
portions, bioink precursors should be stable, reliable, shape fidelity, and maturity of the biostructures during
printable, biocompatible, cytocompatible, biodegradable, and after the printing phase. To overcome these problems,
bioactive, and commercially available. In addition to solubilized decellularized bioink materials can be further
the essential features of bioprinting, bioink should be biofunctionalized with enhancers that are important
organ-specific with regeneration-promoting properties, to synchronously improve the mechanical, rheological,
providing an ideal platform for angiogenesis in culture, and and biological properties of the original bioink. Overall,
avoiding immune rejection after surgical transplantation. crosslinked dECM-derived bioinks can significantly
Nonetheless, highly complex ultrastructural and improve structural stability, cell encapsulation ability,
biomechanical features of ECM vary from tissue to tissue mechanical strength, material bonding, and printability
or organ to organ, which makes it difficult to reconstitute comparable to nondeformable tissues/organs. Recently,
using other natural, synthetic, and semisynthetic the application of conjugated bioinks using decellularized
polymers. Thus, the reconstruction of structural delicacy matrices and gelatin derivatives has attracted much
and complexity of multicellular human organs, mimicry attention. For example, by adding methacrylic acid
of biological mechanism of organ developmental stages, groups to gelatin derivatives, it is possible to synthesize
specialized vascular networks, and innervation patterns dECM-GelMA composites that form hydrogels by
are some of the most critical challenges. Formulation photo-crosslinking via a UV crosslinking mechanism.
of bioink recapitulating the complexity of native tissue/ Crosslinking modification with methacrylic acid has been
organ-specific matrices is still an open challenge. demonstrated to significantly improve the mechanical
integrity of bioinks based on decellularized materials. It is
Fortunately, the emerging concept of using tissue/
organ decellularization technology to design and formulate clear that the preparation of decellularized bioink materials
and their biological, physical, and mechanical integrity
acellular matrix-based cell-laden bioinks provides the is highly dependent on the method of decellularization,
potential toward the biofabrication of specific tissue/ concentration of cell contents, gelation rate, physical,
organ bioequivalents. Briefly, decellularization method has chemical, and enzymatic crosslinking mechanisms.
evolved as an attractive technology for removing cellular
components from source tissue/organ while preserving While 3D bioprinting is undoubtedly the future hope
important constituents of ECM. Decellularized matrix is for automated manufacturing of more stable bioartificial
considered the most biomimetic, reliable, and instructive tissues and organ substitutes within a predictable
biomaterial compared to other natural, synthetic, or timeframe, this technology is still in its infancy. More
synthetic materials for the formulation of translational advanced biomaterials engineering and crosslinking
bioink substrates that can induce or control a vast number strategies to biofunctionalize decellularized matrices with

Volume 9 Issue 3 (2023) 350 https://doi.org/10.18063/ijb.714