Page 94 - IJB-9-6

International Journal of Bioprinting Review of 3D bioprinted organoids

factor (bFGF), and others, can promote angiogenesis and 4.1. Drug screening
development. Compared with other bioinks, dECM has The development of new drugs usually requires a large
been identified as a promising bioink material for vascular amount of cost. Before clinical trials, drugs must be
bioprinting due to its rich composition of proteins and screened for various aspects, such as activity, toxicity,
growth factors. In fact, bioinks based on dECM have metabolism, efficacy, side effects, and dose response .
[95]
been successfully used in vascular bioprinting. Wang et Two-dimensional (2D) cell culture models and
al. combined pancreatic extracellular matrix (pECM) experimental animal models are often used in traditional
with hyaluronic acid methacrylate (HAMA) to develop a drug screening models, but there are many problems with
new bioink. The study confirmed the ability of dECM to traditional drug screening models. The 2D cell culture
promote the formation of new blood vessels . However, model supports the observation of cell morphology at
[91]
the preparation of dECM requires a decellularization the cellular level, but it lacks the interaction between cells
process, during which many growth factors may be and does not simulate the complex in vivo environment.
lost. Therefore, Wang et al. modified the above bioinks Animal models improve complexity, but differences
by combining GelMA, pECM, and platelet-rich plasma between animal and human genomes make animal models
(PRP) to prepare a new bioink that is readily available and inaccurate predictors of drug response, and there are
rich in various growth factors. At the same time, it also ethical and moral controversies associated with animal
has good printability. The improved bioink also showed models [95,96] . Taken together, evaluating a new drug usually
better angiogenic ability . Islet organoids printed by takes 12–15 years, and 50% of new drug development will
[92]
the above two bioinks and DLP technology may have fail due to unpredictable toxic reactions . Therefore, the
[97]
potential application value in islet transplantation. research of an accurate drug screening model is essential.
Noor et al. prepared personalized hydrogel bioink using Bioprinted organoids, highly similar to tissue organs
dECM derived from the omental tissue of patients and in vivo, are widely used in drug screening as an alternative
successfully printed the vascularized heart structure to traditional drug screening models. As many drugs can
in the supporting material. The printed structure cause varying degrees of damage to the liver and kidney,
was extracted from the supporting material through these organs, which are crucial for human drug metabolism
enzymatic hydrolysis or chemical degradation, and this and detoxification, are also important for toxicity tests. In
extraction method did not significantly compromise the addition, bioprinting can also support the application of
cell vitality . high-throughput screening technology and improve drug
[93]
In addition, studies have shown that combining screening efficiency .
[97]
endothelial cells with stem cells or organoids is also Lawlor et al. successfully constructed kidney organoids
an effective method of organoid vascularization. Zhao using extrusion bioprinting technology and tested them for
et al. have developed a new airflow-assisted bioprinting the toxicity of aminoglycosides. This all-purpose antibiotic
technique to print multifunctional helical microstructures can heal infections brought on by Gram-negative germs, but
inside microspheres. Using this technique, they successfully it frequently causes acute tubular necrosis, which damages
created osteoblast-like organs with vascularized spiral the kidneys . Lawlor et al. treated printed kidney-like
[14]
structures, which involved printing endothelial cell spiral organs using aminoglycosides, and cell viability was
structures into bone marrow MSC microspheres. In vitro, estimated by ATP (adenosine triphosphate, a direct source
bone marrow MSCs were induced to differentiate into of energy for vital activities) content after 72 h. The results
osteoblasts, and endothelial cells produced vascularized showed that the activity of the treated cells decreased,
cells . and the decrease showed concentration-dependent
[94]
characteristics, which confirmed that bioprinted organoids
4. Biomedical applications of bioprinted are practical tools used in toxicity test. Bouwmeester
organoids et al. created liver structures using intrahepatic bile duct
cell organoids (ICOs) and extrusion-based bioprinting
With appropriate bioink, bioprinting, and tissue techniques. After printing, the organoids in the structure
vascularization strategies, complex organoids that are maintained relatively stable cell viability for 10 days.
highly similar to tissues and organs in the body can They exposed organoids in the bioprinted structures to
be constructed. To date, bioprinting has been utilized acetaminophen (APAP, a hepatotoxic compound) on the
extensively in drug screening, regenerative medicine, 7th day after printing. After 72 h of exposure, organoid cell
tumor research, and many other areas. Several organoids, activity decreased to 21%–45%, and the organoid shape
including hearts, livers, and kidneys, have been created was damaged, indicating cellular stress. It demonstrated
using this technique (Figure 5). that liver structures obtained by combining organoids

Volume 9 Issue 6 (2023) 86 https://doi.org/10.36922/ijb.0112