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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
                                                                                                      89,182,185,186
            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
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