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International Journal of Bioprinting Printed organoids for medicine

A notable example is the 3D-printed polycarbonate potential of organoid-based platforms in translational
perfusion bioreactor, which supports the simultaneous research.
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culture of hundreds of hepatic organoids under controlled
perfusion. By maintaining consistent metabolic activity for 5.5. Challenges and future directions
up to 4 weeks, these systems address a critical limitation Despite advancements in printing vascular networks,
of traditional static cultures and advance their utility in seamless anatomical and functional integration between
drug metabolism studies. Recent design improvements engineered vessels and organoid-derived microvasculature
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prioritize uniform nutrient delivery, efficient waste remains elusive. Overcoming this hurdle requires
removal, and minimized shear stress, thereby enhancing innovations in two key areas. First, the co-printing of
organoid viability and experimental reproducibility. endothelial cells with angiogenic factors to promote
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vasculogenesis, and second, the development of advanced
To standardize output, another 3D bioprinting platform imaging or sensor-based tools to evaluate vascular
presents a promising alternative. Shin et al. addressed functionality and optimize tissue–tissue interfaces.
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the limitations of optimization of critical process variables Meanwhile, short-term biocompatibility does not
(bioink viscosity, nozzle size, printing duration, pressure, guarantee safety over extended periods, as degradation
and cell density) by leveraging machine learning to byproducts may trigger inflammatory responses or
streamline parameter optimization and enable real-time compromise organoid viability. Future efforts must
prediction of cellular droplet dimensions. This high- prioritize the development of fully biodegradable materials
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throughput bioprinting system was engineered to generate that mimic the dynamic turnover of native ECM while
over 50 cellular droplets per cycle, facilitating the rapid exerting immunomodulatory effects. Concurrently,
compilation of datasets essential for robust algorithmic systematic investigations into the long-term biological
training. Five machine learning models were evaluated for impacts of material degradation are essential to refine
performance, with the multilayer perceptron exhibiting strategies for mitigating adverse outcomes.
superior predictive accuracy and the decision tree achieving Current 3D-printed systems excel at providing
the shortest computational latency. To enhance practical structural frameworks but often fail to induce functional
utility, these optimized algorithms were embedded into maturation, such as the formation of innervated muscle
an intuitive interface designed for seamless integration or vascularized glomeruli. To bridge this gap, researchers
into experimental workflows, which bridges bioprinting must integrate multifaceted stimuli into engineered
automation with data-driven parameter refinement, environments, including mechanical forces, electrical
holding significant potential to advance scalable organoid signaling, and spatiotemporal biochemical gradients.
manufacturing (Figure 6B & C). By harmonizing precision Furthermore, elucidating the molecular and cellular
and efficiency, this framework is poised to synergize with mechanisms governing maturation will inform the design
diverse biomanufacturing technologies, accelerating of targeted interventions.
applications in drug development, disease modeling, and
regenerative medicine. Innovations in artificial intelligence present a
transformative opportunity for clinical translation.
Complementary to perfusion systems, inkjet Artificial intelligence-driven platforms can streamline
bioprinting enables the precise deposition of organoids organoid design through rapid screening, enable high-
onto pre-patterned substrates, forming high-density arrays resolution analysis of multiscale imaging and multi-omics
ideal for large-scale screening. A 96-well plate format datasets, and facilitate precise preclinical drug testing
with printed ECM microdots, for instance, facilitates and disease modeling. Achieving clinical relevance also
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uniform culture of intestinal organoids and accelerates demands rigorous standardization. Scalable production
high-throughput toxicity testing of anticancer agents. 222,223 protocols must ensure precision and reproducibility, while
Such array-based systems significantly streamline drug standardized sterilization, cell seeding, and functional
discovery workflows, reducing time and resource demands validation procedures are indispensable for safe patient
while improving data consistency. applications.
Despite these strides, scaling organoid cultures requires
balancing system complexity with cost-effectiveness. 6. Conclusion
Future innovations in bioreactor design must prioritize Advances in bioprinting have profoundly advanced our
scalability, automation, low-cost accessibility, computer comprehension of organoid and tumoroid development,
numerical control-driven platform, and integration with regeneration, pathophysiological mechanisms, drug
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artificial intelligence-driven analytics to fully unlock the sensitivity assessment, and clinical translation.

Volume 11 Issue 4 (2025) 87 doi: 10.36922/IJB025190184