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International Journal of Bioprinting Decellularized materials for bioprinting of liver constructs

Keywords: Biofabrication; Bioprinting; Decellularization; the inadequacies associated with currently intractable
Bioink; Liver tissue engineering; Translational regenerative diseases. The original concept of the tissue engineering
medicine research field was formally proposed in a historic milestone
research paper reported in Science by Langer and Vacanti
in 1993, which detailed for the first time the practical
application and properties of biodegradable scaffolds as
1. Introduction a 3D-culture substrate . In classical tissue engineering
[9]
Human body is the most complex and marvelously evolved strategies, living cells, biocompatible scaffolds, and bio-
structure on earth, composed of many different cell types, assistants (growth factors and hormones) are generally
tissues, and organs, performing numerous specialized considered interdependent essential “building blocks”
biological functions. It has a limited capability to properly for the successful manufacturing of tissue-engineered
repair or self-regenerate most, if not all, of its complex products. Recent advances in tissue engineering to repair
tissues and organs when natural biological, structural, and regenerate damaged tissue have attracted significant
or mechanical integrity is severely compromised. interest from transplant clinicians and interdisciplinary
Medical treatment of cell/tissue/organ failure because of researchers. Owing to the outstanding advantages, tissue
cellular damage, impairment of critical tissue function, engineering and regenerative medicine means are arguably
or devastating deficits is a paramount public health the only therapeutic alternatives that apply biological
concern. In the case of vital organs (e.g., liver), lack of and engineering principles to generate tissue or organ
adequate treatment or replacement of damaged organs substitutes with native-like structural and functional
[9,10]
without proper treatment for progressive chronic diseases features . In addition to clinical translations of
means certain death for the patient [1,2] . Tissue/organ bioengineered constructs, other uses include personalized
repair and transplantation are viable options for treating drug screening, drug repositioning, deconvolution of
pathologies in patients with organ dysfunction, depending biophysiological and pathological signals, high-content
[11-13]
on the intensity and severity of the disease or associated analysis, disease modeling, and morphogenesis studies .
complications. Technological advances in cell, tissue, and Contemporary tissue engineering strategies
organ transplantation procedures have proven to help mainly rely on biocompatible porous scaffolds or
improve the overall health of patients and increase survival hydrogels incorporated with living cells and associated
rates while reducing the risk of side effects . However, supplements . However, it is difficult to generate finely
[3]
[9]
scarcity of optimal donors, difficulty in human leukocyte tuned therapeutically relevant biological structures using
antigens (HLA) matching, risk of graft rejection, induction traditional methods. Ultimately, generating multiscale
of postoperative immune intolerance, and the toxicity of functional tissue and organ replacements with sufficient
the lifelong use of pharmacological immunosuppression maturity remains a major obstacle in translational
are some of the daunting issues confronting the field of regenerative medicine [10,17-20] . Therefore, there continues
innovative transplant procedures. Given the significant to be an emphasis on the development and refinement
increase in critical organ dysfunction due to a variety of bioengineering strategies that either use living cells
of aberrant factors, the list of patients waiting for life- exclusively or incorporate biocompatible biomaterials
saving organ transplants is growing significantly at an for the large-scale automated biomanufacturing of
overwhelming rate worldwide. With the alarming increase heterogeneous and fully functional replacements for
in the incidence of end-stage liver failure and the ongoing critical organs such as the liver, kidney, heart, and lung.
disparity between organ supply/demand ratio, transplant Consequently, 3D bioprinting has appeared as a rapidly
clinicians, and researchers are working frantically to growing tool that utilizes computer-aided manufacturing
develop advanced alternative therapeutic approaches to techniques to produce clinically valuable bioinic structures
engineer bioartificial tissue grafts or bioequivalents of with desired biological, structural, and biomechanical
organs [4-8] . complexities for repairing/replacing diseased/damaged

Scientific advances and technological breakthroughs tissues/organs [21-27] .
to recapitulate the biological cascade of native tissues have In this review, an overview of bioprinting technologies,
a broad spectrum of potential biomedical applications. bioink requirements, and fundamentals of decellularization
Thus, the research domains of tissue engineering and methods is explained. Thereafter, we outline the recent
regenerative medicine have boosted as an immediate representative studies for the adoption of liver-specific
response to the urgency of alternative means of developing decellularized materials in the formulation of bioinks for
biologically active three-dimensional (3D) tissue and organ liver tissue bioprinting applications. Finally, the current
surrogates to help save lives as well as to address many of challenges in bioprinting research as well as the future

Volume 9 Issue 3 (2023) 341 https://doi.org/10.18063/ijb.714