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International Journal of Bioprinting Review of 3D bioprinted organoids

affect the functionality of cardiac organoids. It is confirmed islet organoids were still alive, and the mice could recover
that the single organoid model may miss unanticipated regular blood sugar within 60 min after meals, and their
toxicity and side effects in drug screening. weight also showed a rising trend .
[91]
4.2. Regenerative medicine 4.3. Cancer research
Donor shortage and immune rejection have been major Cancer is a severe disease that poses a threat to life, and
medical challenges, with only 10% of the global demand for its morbidity and mortality are increasing. However, the
organs currently reported to be met [100] . At the same time, mechanisms by which cancer occurs and its treatment
the uncertain outcomes of organ transplantation increase are still poorly understood. Patient-derived 2D tumor
the risk of infection. Therefore, how to construct biological culture and xenotransplantation have been widely used
tissues and organs in vitro to improve portability and limit to simulate tumor invasion and therapeutic response.
the risk of immune response is an urgent challenge to be However, 2D models cannot fully summarize biochemical
addressed [100] . Bioprinted organoids, which can replicate and biophysical signals of the tumor environment,
the structure and function of native tissues, have broad and xenotransplantation also has problems such as
application prospects in regenerative medicine and can be genetic variability [102,103] . An ideal model for studying
used as organ transplant donors. tumors is an organoid that mimics the histology,
Xie et al. induced callus organoids generated by immunohistochemistry, and genetic heterogeneity of
bioprinting in vitro and transplanted the callus organoids tumors but does not contain the mesenchymal cellular
into a 5 mm × 4 mm cylindrical defect at the distal end elements and intercellular connections found in the actual
of the rabbit femur. Four weeks after implantation, they tumor tissue. In this regard, bioprinting technology can
observed that the callus organoids promoted the formation precisely control the distribution of cells and biomaterials,
of new bone, and the newly generated bone tissue almost mimicking the spatial and chemical distribution of natural
filled the defect site. Compared to the 2–3-month recovery tissues, and therefore has great potential for applications in
time required in traditional tissue engineering, bioprinting building complex tumor models and reconstructing tumor
offers a faster solution for bone repair, achieving rapid microenvironments [104] .
bone healing . Adine et al. used magnetic bioprinting Gong et al. generated bladder tumor organoids with
[72]
technology to print salivate glands (SG) organoids and acoustic bioprinting and murine-derived bladder tumor
transplanted SG organoids into an in vitro model. After cells. The printed organs had a survival rate of more than
transplantation, SG organoids were found to significantly 85% and maintained an immune milieu comparable to the
stimulate the epithelial and neuronal growth of damaged original tissue for 2 weeks. In addition, after 2 days of co-
SG, which is of great significance for treating dry mouth culture of printed organoids and autologous lymphocytes,
syndrome .
[52]
they observed the generation of tumor-specific T cells
Yang et al. bioprinted liver organoids using HepaRG that can kill tumor organoids, suggesting that bioprinted
cells, and the printed organoids obtained liver functions organoids can be used for individualized immunotherapy .
[51]
such as albumin secretion, drug metabolism, and glycogen Chen et al. used the same printing technique to print patient-
storage 7 days after differentiation. They transplanted derived microtissues (PDMs, consisting of colorectal tumors
liver organoids into F/R mice (a modulated model of liver and healthy organoids derived from colorectal cancer (CRC)
damage that inhibits immune rejection, where deletion of patients), simulated tumor invasion in CRC patients, and
the Fah gene leads to the accumulation of toxic tyrosine demonstrated the application of PDMs in drug screening [103] .
metabolites in liver cells that cause liver damage). They In drug screening, two drugs (5-FU and Erbitux, the drugs
found that the liver organoids matured further and for the treatment of colon cancer disease) were selected, and
formed functional blood vessels. After transplantation, the organoids were tested under different drug concentrations.
survival period of mice was significantly prolonged, and Then, the distance between the tumor and healthy organs
the degree of weight loss was reduced, confirming that served as a measure of tumor invasion potential. The results
the transplantation of liver organoids could alleviate the showed that organoids were more sensitive to Erbitux. As
liver failure of animals and has the potential to be used as long-term cultured bladder organoids lack vital components
organ transplant donors [101] . It is worth mentioning that of a normal bladder (such as tissue matrix and muscle
the bioprinted liver organoids contain functions such as layer), Kim et al. proposed the assembly concept to tackle
protein secretion, which may have potential applications in the problem. They successfully constructed bladder tumor
the production of biological agents. Wang et al. implanted assembly through bioprinting technology, combined with
islet organoids based on HAMA/pECM bioink bioprinting patient-derived bladder tumor organoids, endothelial cells
into diabetic mice. After 12 weeks of implantation, the (HULECs), and patient-derived cancer-related fibroblasts

Volume 9 Issue 6 (2023) 88 https://doi.org/10.36922/ijb.0112