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International Journal of Bioprinting dECM bioink for in vitro disease modeling

bioink and spinning conditions helped generate liver et al. developed a practical co-culture system featuring
spheroids and improve certain functions of the spheroids, independently adjustable sections for various cell
such as albumin secretion. Additionally, a liver injury types via core-shell bioprinting. Although multiple
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model was created via treatment with transforming types of cells that constitute the liver were successfully
growth factor-beta (TGF-beta), an inducer of epithelial- arranged on one platform in three dimensions to mimic
to-mesenchymal transition. The cells were treated with the liver’s microenvironment, they were faced with the
N-acetylcysteine (NAC), a therapeutic agent, to confirm constraints in creating an intact liver-specific structure.
the function of the model and its potential as a platform for In particular, current 3D bioprinting technology is
drug testing. The model contained a hexagonal structure limited to implementing complex vascular mimetics in
featuring a liver-specific microenvironment, mimicking a various sizes, including cells, on one platform; therefore,
complex 3D liver structure. Furthermore, because of the producing a perfect sinusoid structure is not feasible
spinning conditions, the model allowed fluid flow and using this technology. Additionally, to implement the
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could deliver sufficiently accurate data after drug screening. pathophysiological mechanisms of various liver diseases
However, the cell sources that can be employed to create in these models, crosstalk between liver and different
this 3D model are rather limited, and the model features organ compartments via vascular mimetics is essential.
an exceedingly simple structure that could not effectively Therefore, the development of 3D bioprinting technology
mimic sinusoidal structures. Furthermore, inducing blood that allows for the versatile fabrication of functional
flow and tissue crosstalk within the model is difficult due vascular mimetics of various sizes at the desired locations
to the absence of vascular mimetic structure. within in vitro models is necessary. 188

Lee et al. were the first to develop an LdECM bioink, Owing to the variations in genetics and lifestyle, the
in which they encapsulated various hepatic cells, and types and manifestations of liver diseases vary among
with which they fabricated a normal in vitro model patients, accentuating the needs for personalized
using extrusion-based 3D bioprinting. 181,185 Based on the 3D-bioprinted liver models tailored to the clinical
normal liver model fabrication technology, an in vitro requirements of patients. Thus, a 3D bioprinting
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liver fibrosis model was created via the encapsulation of technique that can create liver models stably using
activated stellate cells, which are liver-inducing factors, patient-specific or individualized liver-derived stem cells
in gelatin to induce liver fibrosis (Figure 4B). A model is urgently needed to accurately simulate the mechanism
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was created using most of the cell types constituting the of occurrence and progression of liver disease in each case.
sinusoid structure, and a multilayered sinusoidal structure Yang et al. have attempted in creating a liver structure
was fabricated by extrusion-based 3D bioprinting using using hepatorganoids via 3D bioprinting technology,
the gelatin bioink as the sacrificial material. Additionally, and various research teams have fabricated liver models
a microfluidic channel was incorporated into the model; using liver cell lines and primary cells. However, liver
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therefore, it was possible to simulate blood flow in a models 3D-bioprinted with liver-derived cells obtained
sinusoidal structure. Hallmarks of liver fibrosis, such from patients are hitherto unavailable. Thus, there is
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as collagen accumulation, apoptosis, and liver fibrosis- an urgent need to develop a 3D-bioprinted liver model
specific marker expression, were conspicuously featured using liver-derived cells. These personalized models may
in this model. The model created in this study is contribute to the development of personalized treatment
significant as it was able to mimic most liver functions and prevention strategies.
by precisely expressing the sinusoidal structure and liver- The liver functions in a dynamic environment.
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specific microenvironment, and it could be employed Therefore, to simulate the functions of a real liver, it is
as a liver fibrosis model. Since the progression of liver necessary to develop a chamber that mimics blood flow,
fibrosis requires crosstalk among multiple organs, this in fluid dynamics, mechanical stress, etc., and combine it
vitro liver model is unable to recapitulate the interactions with a 3D-printed liver model. In addition to reproducing
between the specific tissues and organs. Nevertheless, the structure and functions of the liver, the 3D-bioprinted
this study successfully created a drug testing platform model must be able to mimic the biochemical reactions
for liver fibrosis, paving the way for further research and of the liver. To achieve this, analysis of multi-omics
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development of drugs for liver diseases.
data, including those pertaining to RNA, proteins, and
Although liver models that successfully simulate many metabolites, is required to help understand the complex
functions of the liver in vitro have been developed using physiological responses of liver models. Shinozawa et
3D bioprinting and various hydrogels, including LdECM, al. recently developed a high-fidelity in vitro model
there are still many areas that require improvement in using human pluripotent stem cell-derived organoids
terms of fabrication and application. Recently, Taymour for the purpose of studying drug-induced liver injury.
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Volume 10 Issue 2 (2024) 148 doi: 10.36922/ijb.1970