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International Journal of Bioprinting Printed organoids for medicine

that mitochondrial transfer from normal mammary role of bioprinting in capturing the dynamic crosstalk
epithelial cells to breast cancer cells plays a role in the within the TME, which drives drug resistance and tumor
redirection process. Their results demonstrate that progression. Additionally, the incorporation of neural cells
mitochondrial transfer contributes to microenvironmental and lymphatic analogs into bioprinted models has revealed
redirection of cancer cells through alteration of metabolic insights into tumor innervation and immune evasion
and molecular functions of the recipient cancer cells, which mechanisms. 39,159 These models also capture cytokine-
is the first description of a 3D bioprinter-assisted organoid mediated crosstalk, such as CAF-driven ECM remodeling
system for studying mitochondrial transfer. Furthermore, and immunosuppressive signaling, which are pivotal for
these studies are also the first mechanistic insights into drug resistance studies. 121
the process of mammary microenvironmental redirection
of cancer, providing a framework for new therapeutic 4.2. High-throughput tumor organoid auto-printing
strategies to control cancer. Khan et al. introduced a for drug screening
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human bone marrow organoid capable of sustaining the Conventional organoid cultures face challenges in terms
proliferation of primary cells derived from individuals of batch-to-batch variability and labor-intensive protocols.
with myeloid and lymphoid hematologic malignancies. Automated bioprinting systems, however, ensure
This model facilitates in-depth investigations into the consistent deposition of cells and bioinks, enabling mass
pathophysiology of blood cancers within their TMEs and production of uniform tumor organoids, which greatly
offers a valuable ex vivo platform for evaluating novel avoids the bias caused by operators’ manipulation. 78,159,164
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therapeutic agents. Chen et al. generated colorectal Kim et al. engineered a fully automated workstation that
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cancer microtissues based on patient-specific colonoscopy streamlines the entire workflow from tissue dissociation to
images by printing photodynamic therapies enclosed by drug screening, achieving a 20-fold increase in processing
healthy organoids to mimic the tumor’s interaction with efficiency. Capable of handling 200 specimens per run,
adjacent normal tissue. The in vitro response of these this system eliminates manual variability while enabling
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microtissues to standard 5-fluorouracil therapy mirrored large-scale phenotypic and molecular profiling. Hou
patient responses, suggesting the model’s potential as et al. engineered a high-throughput screening-compatible
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a physiologically relevant platform for drug screening. approach that standardizes organoid generation in
Furthermore, the model enabled the calculation of patient- conventional flat-bottom 384- and 1536-well plates. This
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specific risk for tumor invasion into neighboring tissues by method integrates magnet-assisted bioprinting technology
assessing the quantity and proximity of invading tumor cells. with cell-repellent surface engineering to ensure precision
This approach offers a real-time quantitative assessment and scalability. To demonstrate its applicability in
for studying cancer advancement and metastasis. automated drug discovery workflows, the researchers

In a recent study, microtissues comprising patient- conducted a pilot cytotoxicity assessment of approximately
derived lung tumoroids were co-cultured with 3300 clinically approved compounds. The results
corresponding CAFs and endothelial cells. The process underscore the platform’s breakthrough to facilitate large-
involved printing vessel structures, seeding CAFs, scale drug screening through patient-derived 3D oncology
and subsequently printing tumoroids suspended in a models. By enabling robust analysis of clinically relevant
hydrogel sourced from porcine lung tissue into the same tissues, this innovation represents a critical advancement
compartment. Notably, an active fusion between stromal toward personalized therapeutic development.
cells and tumoroids occurred, leading to the formation of For personalized medicine, bioprinted constructs using
microvessels that directly engaged with other cell types. patient-derived cells have been utilized to predict drug
Upon administering the drug poziotinib through the vessel responses. In head and neck squamous cell carcinoma,
structures, it was observed that both endothelial cells and bioprinted models maintained epithelial phenotypes and
CAFs, along with the CAF-secreted matrix, shielded the exhibited reduced cytotoxicity to radiochemotherapy
lung tumoroids from the treatment. Consequently, this compared to spheroids, better reflecting clinical resistance
model holds promise for investigating the impact of cell– patterns. 166,167 Ovarian and colorectal tumor models
cell and cell–matrix interactions on the effectiveness of bioprinted with nanocomposite hydrogels were screened
drug delivery to tumor tissues. 163 for gemcitabine and oxaliplatin responses, revealing drug-
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In ovarian cancer models, bioprinted microtumors specific resistance mechanisms. These advances highlight
composed of leukemia (HL-60) and stromal cells the potential of automated bioprinting to generate patient-
exhibited dynamic cell–cell interactions, where stromal specific organoids at scale, bridging the gap between in vitro
cells modulated cancer cell proliferation and invasion assays and clinical outcomes. Tebon et al. introduced
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through cytokine signaling. Such models underscore the an integrated platform combining bioprinted tumor

Volume 11 Issue 4 (2025) 82 doi: 10.36922/IJB025190184