(i) Liver diseases such as cirrhosis, hepatitis, and liver cancer are among the leading causes of

death worldwide, and current treatment these options for conditions are limited. Recent
breakthroughs in bioink 3D printing technology, on the other hand, hold considerable potential
for meeting these therapeutic needs. Bioink 3D printing uses biocompatible materials and
living cells to build three-dimensional structures that mimic the function of real tissues. Bioink
3D printing technology can be utilised to build liver organs that can be transplanted into
patients to help provide functional damaged liver tissue in cases of liver disease. These liver
blotches can be tailored to the patient's individual liver anatomy, and they have the potential to
improve liver transplant outcomes while reducing the need for organ donors. The bioink can
also be used to produce liver models for drug testing and toxicity research, which can improve
the safety and efficacy of drugs [1]. However, there are still limitations that need to be
addressed, such as difficulty in creating large-scale functional liver tissues, and ensuring the
bioink does not trigger an immune response. The placement of the transplanted tissue is also a
challenge. Researchers are working with a keen interest in optimizing the technology for
clinical use [2].
(ii) The variables in how bioink 3D printing technology can be applied to liver diseases include
delivery method, specific design choices such as cell type, and scaffold material. One important
variable in applying bioink 3D printing technology to liver diseases is the delivery method of
the bioink into the patient's body. One approach is to transplant the 3D printed liver tissue into
the patient's liver, either through a surgical procedure or by using a catheter to inject the tissue
directly into the liver [3]. Another approach is to use the bioink to create a liver patch that can
be placed over damaged areas of the liver to provide support and stimulate regeneration. The
third most promising variable is the choice of scaffold material, which can influence the
behavior and function of the printed liver tissue. Researchers are investigating various scaffold
materials, including natural polymers, synthetic polymers, and hybrid materials, to optimize
the growth and function of the printed liver tissue [4-5].
(iii) Although the liver is essential for metabolism, in vitro human liver models using 2D or
suspension cultures of primary hepatocytes rapidly lose function. This restricts medicine
development and research into organ failure [6-8]. Several models, including the
micropatterned model, 3D transwell cultures, spheroid 3D models, and scaffold-free 3D bio-
printing models, can sustain drug metabolism function for a longer period of time [9]. The
micropatterned model is the most intriguing since it partially replicates liver damage and
metabolite production found in pharmaceutical company clinical studies. In comparison to
other models, it is a revolutionary technology [10-11].
(1V) There are various impediments to clinical use of bioink 3D printing for liver organ
replacement. One of the most significant practical obstacles is the discovery and fabrication of
appropriate bioink materials capable of mimicking the intricate architecture and function of the
liver. To optimize the bioink compositions and printing conditions, substantial research and
development are required. Another key impediment is the cost of developing, manufacturing,
and delivering bioink-based liver tissue, which may be prohibitively expensive for some
patients or healthcare systems. The regulatory approval process might also be expensive.
difficulties about the use of animal-derived or synthetic ingredients in bioink formulations may
generate ethical difficulties, raising questions about the technology's ethical implications [12-
13].
(v) For solving the unmet clinical demand for liver transplantation, there are numerous
alternatives to bioink 3D printing. The use of stem cell-derived liver cells is of these
alternatives.
Pluripotent stem cells are differentiated into hepatic cells to produce stem cell-derived liver
cells. In preclinical investigations, this technique has showed promise as a potential treatment
for liver disorders and as a supply of liver tissue for transplantation. Human pluripotent stem
cells were employed to create functional liver tissue in a mouse model of liver failure in a work
by Hassan et al. [14]. The study proved the feasibility of using stem cell-derived liver cells for
liver regeneration and transplantation. Liver organoids, on the other hand, are three-
dimensional structures that mimic the microenvironment of the liver. These structures are
typically generated from primary liver cells or stem cell-derived liver cells and can be used to
study liver disease and drug toxicity. In a study by Takebe et al. [15], human liver organoids
were generated from pluripotent stem cells and shown to express key liver functions.
However, in terms of cost, stem cell-derived liver can impact the adoption of bioink 3D
printing, but we cannot manufacture huge liver structures using this technology. Thus, stem
cells have a financial advantage while having a disadvantage in terms of liver organ structure.
Thus, the acceptance of 3D bioink printing may be influenced by the medical conditions in
clinical trials stem cell derived lever [16].

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