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International Journal of Bioprinting dECM bioink for in vitro disease modeling

stenotic, and tortuous arteries. These arteries are able to functionality. Electrical stimuli are used because they affect
recapitulate the pathophysiologic facets of atherosclerosis, the heart rate. Bouchard et al. reported that maturation
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such as inflammatory stimuli, hyperlipidemia, and of human iPSC-derived cardiomyocytes in fibrin hydrogel
turbulent flow. Thus, 3D bioprinting is a useful approach to can be accelerated using electromechanical signals.
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building various tubular structures for models mimicking In summary, engineered cardiovascular models can be
hemodynamically regulated pathological conditions. These improved with tunable dECMs and bioprinting, and their
models can be adapted for drug screening and disease maturation can be induced with external stimuli. These
prediction in models created with patient-derived cells. cardiovascular models can be applied to various CVDs.
Possessing microstructure of cardiac tissue, which is 4.3. Liver tissue-derived decellularized
essential for understanding cardiac physiology, is another extracellular matrix
strength of 3D in vitro cardiac models. Cardiotoxicity The representative organs of the digestive system are
is commonly cited as the one of the major reasons for stomach, liver, and intestine, among which the liver plays
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drug failure. Among post-approval drugs, 45% have an important role in regulating the overall metabolism,
been withdrawn owing to cardiotoxicity. In addition, including blood sugar control, and processing and storage of
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the physiology of the animal heart differs from that of body substances. Additionally, the liver makes and stores
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the human heart. For example, the resting heart rate of various nutrients necessary for the body, such as proteins,
humans is between 60 and 100 bpm; in comparison, the participates in carbohydrate, fat, hormone, vitamin, and
animal models for clinical experiments (e.g., mice, rabbits, mineral metabolism, and detoxifies harmful substances.
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and dogs) have much higher heart rates, measuring However, diverse as these functions are, the list of known
120–500 ppm. Thus, a humanized cardiac model is liver diseases, such as hepatitis, liver cancer, and alcoholic
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indispensable for assessing drug toxicity in the context of and non-alcoholic fatty liver disease, is similarly varied.
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human physiology. From this viewpoint, a cardiac dECM Particularly, fibrosis and cirrhosis may develop in the liver,
can simulate the sophisticated cardiac ECM network, resulting in homeostasis disruption and organ failure.
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and 3D bioprinting can aid in forming specific cardiac Fibrosis occurs only in certain organs, such as liver, lungs,
microstructures. 160,161 Das et al. bioprinted cardiac tissue and heart. Since liver transplantation is the only feasible
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models with a heart dECM (hdECM). Cardiomyocytes treatment for severe liver damage, it is essential to develop
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in the hdECM differentiated into cells with a stretched new therapies and in vitro models to test these therapies.
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morphology, whereas the cells in the collagen exhibited Additionally, simulating various liver functions in vitro
irregular morphologies. In particular, upregulated has important implications for tissue engineering, liver
expression of heart-specific proteins in the bioprinted regenerative medicine, and drug development. 75
cardiac tissue indicated that the dECM and bioprinted The traditional in vitro liver modeling entails the step
models had enhanced tissue-specific characteristics.
of culturing liver cells in two dimensions, which can
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As such, bioprinted cardiovascular models can be used be conducted with sandwich culturing of hepatocytes
in disease mechanism investigations and drug testing. or different co-culture methods involving multiple
To build more reliable cardiac tissue models, additional cell types. These traditional in vitro liver models are
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biological strategies can be applied to bioprinted models. relatively simple in design, allow for adjustment of
The bioprinted cardiovascular models can be improved by experimental conditions, and are convenient for operation
tuning the mechanical properties of the bioink to match during experiments. They are also used for evaluating
the native tissue’s properties and by enhancing maturation drug metabolism and toxicity and for early assessment
orchestrated by external stimuli. To simulate heart- of drug effectiveness and safety. However, the 2D culture
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specific mechanical stiffness, dECM bioink can be modified is faced with challenges in mimicking hepatic sinusoid
with biocompatible polymers. Shin et al. developed tuned heterogeneity, cell density under in vivo condition, and liver
cardiac dECM bioink with laponite and PEG-DA. The circulation. To solve these problems, various 3D in vitro
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biomaterials incorporated with dECM bioink exhibited liver models have been developed. To create a successful
a higher compressive modulus and stable shape fidelity. 3D in vitro liver model, it is important to mimic a liver-
This tuning strategy can extend the application of cardiac specific sinusoidal structure with functional maturity.
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dECMs to various disease conditions, facilitating the The sinusoids are composed of various cells, including
fabrication of healthy and fibrotic heart models. In liver sinusoidal endothelial cells, hepatocytes, hepatic
addition, applying external stimuli to the cardiac models stellate cells, and Kupffer cells. There are two fluidic
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can enhance maturation. The commonly used cell sources channels consisting of the above-mentioned cells in the
are derived from iPSCs or animal-derived cells, which sinusoids within the 3D microenvironment of the ECM.
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are immature cells that do not fully recapitulate cardiac Various approaches have been attempted to simulate the

Volume 10 Issue 2 (2024) 146 doi: 10.36922/ijb.1970