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International Journal of Bioprinting Printed organoids for medicine

perfusable microvasculature, mimicking the blood–brain evaluation of anticancer drug efficacy while also enabling
barrier and neuronal degeneration. These models enable the exploration of personalized cancer therapies.
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the study of amyloid-β aggregation and tauopathy in a
3D microenvironment. Moreover, bioprinted midbrain 4.1. Tumor biology-based bioprinting of tumor-like
organoids containing dopaminergic neurons have been organoids
used to evaluate mitochondrial dysfunction and oxidative 3D printing enables the reconstruction of quasi-native
stress in Parkinson’s disease. 84,123 Wang et al. aimed to spatial topological relationships among different cell
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create a Corti organoid using 3D bioprinting, integrating types within tumor tissue components. This primarily
a “3D culture scaffold + multiple induction signals + inner involves the first-level tumor cell components and specific
ear stem cells.” This approach addressed the limitation of structures, particularly those located on the periphery of the
regenerated hair cells in forming functional ciliary bundles tumor cells, such as immune cells, blood vessels, lymphatic
and establishing synaptic connections with spiral ganglion vessels, nerves, and paracancerous cells. Using 3D printing
cells in a 2D system, hindering the achievement of effective technology, a complex co-culture model with three or
physiological repair of hearing. Their study demonstrated even multiple components can be established based on
that the organoids facilitated the adhesion and proliferation predefined spatial positioning and cell composition ratios.
of inner ear stem cells, leading to the generation of both Additionally, the spatial arrangement of different clones
hair cells and nerve cells. This work presents a promising between tumor cells and their biological interactions
avenue for investigating auditory cell regeneration and warrants further emphasis. Such intricate constructs of
repairing hearing loss. 135 tumor-induced organs or organoids cannot be achieved
by conventional methods and necessitate the use of 3D
3D bioprinting of organoids has significantly advanced bioprinting. Bioprinting technologies have revolutionized
disease modeling by combining stem cell self-organization the fabrication of tumor organoids by enabling precise
with engineered architectures. While challenges remain spatial control over cellular and extracellular components,
in replicating the full complexity of human tissues, thereby recapitulating the heterogeneous architecture
recent innovations in vascularization, 123,125 multicellular of native tumors. This approach addresses the critical
patterning, and biomaterial design are bridging these limitations of conventional organoid models, which often
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gaps. 25,121 Future efforts should focus on integrating fail to mimic the multicellular complexity and spatial
dynamic stimuli, such as mechanical forces and immune organization of TMEs. 25,99
cues, to further enhance pathophysiological relevance. 106
4.1.1. Spatial arrangement of tumor niche
4. Bioprinting tumor organoids: The spatial heterogeneity of tumor subclones and their
simulacrum or throughput dynamic crosstalk with stromal components, driven by
genetic and epigenetic variations, constitute a hallmark
Bioprinting technology can recreate the spatial topological of cancer progression and therapeutic resistance. Single-
relationships between different cellular components cell and spatial transcriptomic analyses reveal that intra-
within tumor organoids, including immune cells, CAFs, tumoral heterogeneity in gastric cancer arises not only
and vascular and lymphatic structures, thus reproducing from genetic diversity but also from spatially organized
the heterogeneous structure of the primary tumor. interactions between proliferative/invasive cancer cells
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Emerging platforms such as organ-on-a-chip, organoids, and tumor-associated fibroblasts, 139,140 among which CAFs
and bioprinting within micro-physiological systems are emerge as central orchestrators. CAFs secrete transforming
increasingly employed to elucidate these interactions. growth factor-beta and matrix metalloproteinases to
These systems accurately recapitulate key features remodel the ECM, thereby creating biomechanical niches
of tumor microenvironments (TMEs) and immune that promote immune evasion and chemoresistance.
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responses, offering physiologically relevant platforms for Multi-material bioprinting strategies enable the
investigating cancer progression, immune evasion, and integration of tumor cells, patient-derived CAFs, and
therapeutic interventions. In addition, the application immune cells into predefined geometries, mimicking the
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of bioprinting technology has been extended to high- in vivo spatial hierarchy observed in solid tumors. 42,99,142,143
throughput screening in tumor model systems. Tumor Studies have elucidated how CAF-secreted interleukin-6
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organoids, which can be produced at scale and tested and C-X-C motif chemokine ligand 12 gradients drive
systematically through automated bioprinting processes, epithelial-mesenchymal transition in breast cancer
play a pivotal role in drug development and personalized organoids, while nanoparticle-mediated targeting of
treatment strategy optimization. The advancement of fibroblast activation protein enhances T-cell infiltration in
this technology has facilitated more rapid and precise murine models. 144,145 Such models have captured dynamic

Volume 11 Issue 4 (2025) 80 doi: 10.36922/IJB025190184