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International Journal of Bioprinting 3D bioprinting for organoid-derived EVs

tissue constructs with strong mechanical properties and 2.3. 3D-bioprinted patient-derived organoids in
is ideal for fabricating organoids such as liver, kidney, precision medicine
and intestinal models. For instance, the Dokmeci group
successfully bioprinted organoids comprising hepatocytes 2.3.1. Patient-derived organoids in precision medicine
and fibroblasts within methacrylated gelatin hydrogels, PDOs have significantly impacted cancer research and
showcasing the potential of extrusion-based printing therapy by enabling the modeling of patient-specific
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in generating functional tissue models. Despite its responses to treatments. These 3D cultures accurately
advantages, extrusion-based bioprinting does have replicate the genomic and histological characteristics of
the original tumors, proving to be crucial for personalized
limitations. The technique exposes bioinks to high pressure cancer medicine. The tumor organoids developed
and shear stress, which can potentially damage cells and from various cancer types, including prostate cancer,
impact their viability. Moreover, the resolution of extrusion- gastrointestinal cancer, breast cancer, and ovarian cancer,
based bioprinting is typically lower compared to those of have shown effectiveness in preclinical drug testing and
other methods such as inkjet or photocuring bioprinting. co-clinical trials. 63–66 PDOs provide several advantages,
To address these challenges, careful optimization of bioink such as the capacity to generate organoids from small
properties is essential to balance viscosity and mechanical tumor samples like needle biopsies and from different
characteristics for successful printing and to maintain regions within the same tumor, facilitating the exploration
cell viability. 59,60 of tumor heterogeneity. These models have the potential
Photocuring bioprinting, also known as light-projection to screen anti-cancer drugs, optimize immunotherapy, and
bioprinting, is a technique that utilizes light to solidify identifying prognostic biomarkers. 67
light-sensitive crosslinkers into 3D shapes without the The integration of PDOs in precision medicine has
need for nozzles. This method is advantageous as it reduces enabled the modeling of various diseases and drug
shear forces on cells, thereby ensuring high cell viability. responses, providing a platform for personalized treatment
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There are two main photocuring bioprinting methods strategies. In the context of genetic diseases, Schene et al.
used to construct organoids: volumetric bioprinting and demonstrated the utility of prime editing in repairing
digital light processing (DLP) bioprinting. Volumetric genetic defects within PDOs, showcasing the precision
bioprinting employs optical tomography to rapidly create and therapeutic potential of this gene editing strategy.
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intricate 3D structures, such as supportive scaffolds for Additionally, the combination of CRISPR genome editing
organoids, which can enhance their functionality. For (knock out, base, or prime editing) with 3D organoid
example, Bernal et al. utilized volumetric bioprinting to cultures has facilitated the modeling of disease progression
create 3D structures with biocompatible resins that support and the study of genetic diseases, bridging the gap between
liver organoids, providing a robust platform for biomedical patient-derived cells and disease understanding. 69,70
research. On the other hand, DLP bioprinting uses visible In specific cases like Leigh syndrome, an incurable
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or ultraviolet light to solidify photosensitive resins layer- mitochondrial disease linked to a SURF1 mutation, Cas9
by-layer onto the print head, allowing for high-speed genome editing was applied to correct the mutated SURF1
printing of detailed 3D structures. Grix et al. demonstrated gene within PDOs, shedding light on the physiological
the use of DLP bioprinting to create liver organoids with connection between SURF1 and Leigh syndrome.
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perfusable channels, which possessed increased viability Furthermore, patient-derived iPSCs have been employed
and improved biofunctionality compared to traditional to model macrocephaly/autism phenotypes, showcasing
monolayer cultures. Photocuring bioprinting offers the versatility of PDOs in studying complex genetic
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high speed and resolution, making it ideal for creating conditions. 72,73 Moreover, the CRISPR-Cas9 system has
intricate and complex structures. However, it is limited to been applied in brain organoid models to induce congenital
photosensitive resins and crosslinkers, and the equipment nervous system malformation disease models, aiding the
required is costly. study of these complex disorders. 74
Understanding the trade-offs associated with In the context of cystic fibrosis, forskolin-induced
these different bioprinting techniques is crucial for swelling in healthy organoids contrasts with the lack
selecting the most suitable method based on the of swelling observed in intestinal organoids derived
specific requirements of the organoid model and from cystic fibrosis patients carrying the F508 deletion
its intended application in disease modeling, drug mutation in the CFTR gene. However, the introduction
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screening, or regenerative medicine. Further research of adenine base editing and the prime editing by the
and development will improve the application of these Geurts group facilitated genetic and functional repair in
technologies in organoid printing. PDOs with CFTR mutations, showcasing the potential of

Volume 10 Issue 5 (2024) 102 doi: 10.36922/ijb.4054