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International Journal of Bioprinting Printed organoids for medicine
organoids with label-free, time-resolved imaging using or sarcoma cells with hyaluronic acid-collagen bioinks,
high-speed live cell interferometry and machine learning- printing them onto gelatin-coated wells, and subsequently
driven analytical tools (Figure 6A). Bioprinting generates replacing the gelatin with culture medium. Alternatively,
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3D tumor structures that preserve native histology and acoustic bioprinting has been used to deposit small
transcriptional profiles. Coupled with high-speed live droplets onto hydrophobic substrates, generating bladder
cell interferometry, this system enables non-invasive, cancer-derived tumoroids containing both cancer cells and
parallelized mass quantification of thousands of organoids CAFs. This approach enables the scalable production
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over time. Machine learning algorithms further enhance of uniform tumoroids that recapitulate the TME while
segmentation accuracy and phenotypic classification. They remaining compatible with high-throughput drug
also demonstrated the platform’s ability to distinguish screening for personalized therapy. While 3D bioprinted
organoids exhibiting transient or persistent sensitivity models enhance reproducibility in drug testing and
versus resistance to targeted therapies. This approach facilitate the study of multicellular interactions in a 3D
provides a scalable framework for resolving temporal and context, they remain static systems. Consequently, they fail
heterotypic adaptations in tumor populations, offering to incorporate dynamic mechanical forces (e.g., fluid flow)
actionable insights to accelerate personalized therapeutic or chemical gradients, both of which critically influence
decision-making. Nonetheless, shortcomings exist in cost tumor cell behavior in vivo. 176
constraints, the availability of specific cell types, the time
needed for model establishment and growth, and success 5. Beyond organoids: three-dimensional-
rates. Parallel innovations in miniaturization have redefined printed biocompatible accessories
screening economics. Phan et al. pioneered a nanoscale The convergence of 3D-printed biocompatible accessories,
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microplate platform (200 nL/well) coupled with artificial like artificial intelligence-driven design, organ-on-chip
intelligence-driven hyperspectral imaging, permitting technologies, and organoid morphology recognition and
simultaneous evaluation of 1536 drug combinations per deconvolution, enhances the functionality and realism
assay. This approach reduces reagent consumption and of the models, enabling intelligence and automation in
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operational costs to 20% of conventional methods without the construction of high-fidelity organoid models. 177–179
compromising data resolution. Individual models vary in This section explores the role of functional biocompatible
their representation of important features such as tumor accessories beyond 3D-printed organoid culture, focusing
heterogeneity, spatial interactions between tumor and on structural supports, functional interfaces, and integrated
stromal microenvironments, metabolic and nutritional systems that augment organoid utility. By leveraging
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gradients, and immunological responses. Consequently, a advanced biomaterials, innovative printing techniques,
strategic integration of diverse models may be necessary and interdisciplinary engineering, these accessories bridge
to enhance the efficacy of clinical studies by bolstering the the gap between in vitro organoids and in vivo physiological
foundation of preclinical data. complexity, opening new frontiers in precision medicine,
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Long-term organoid modeling enables complex tissue engineering, and regenerative therapy. 181,182
therapeutic screening. However, technical challenges
include limited user-friendliness in long-term dynamic cell 5.1.icrofluidic devices for perfusable cultures
culture, incompatibility with rapid cell encapsulation in Microfluidic systems mimic the physiological flow of body
biomimetic hydrogels, and low throughput for compound fluids, allowing precise control of nutrient delivery, shear
stress, and waste removal.
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3D bioprinting facilitates
screening. To address these issues, a micro-solenoid valve-
driven bioprinting system was developed by Joshi et al. the fabrication of complex microchannels with integrated
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This system fabricates the alginate-encapsulated Hep3B sensors or valves, creating organ-on-a-chip platforms
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liver tumor spheroids in a 144-well plate, achieving rapid that combine organoids with fluidic networks.
3D-printed microfluidics can also create chemical
biomimetic tissue formation for large-scale compound gradients (e.g., oxygen, growth factors) to guide organoid
screening.
morphogenesis. Researchers have employed printed
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Bioprinting offers applications beyond TME- gradient chambers to induce regional differentiation in
mimicking models, including standardized cell dispensing hepatic organoids, forming distinct zones of hepatocytes
for high-throughput studies. A key limitation, however, and cholangiocytes, similar to native liver lobules. 188,189
is the tendency of bioinks to spread within small wells, Such spatial control over microenvironments is crucial
compromising the structural integrity required for 3D cell for modeling organ-level functional zonation. 82,190 Recent
culture. To address this issue, researchers have employed advancements in 3D printing technology have enabled
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strategies such as mixing patient-derived glioblastoma the creation of more complex gradient-generating devices,
Volume 11 Issue 4 (2025) 83 doi: 10.36922/IJB025190184