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scenarios, advantages, and limitations. PDMS microfluidics excel in constructing TME
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components , enabling spatiotemporal drug delivery control, and culturing spheroids
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with concentration gradient generation (CGG) to simulate nutrient and drug transport.
However, it faces challenges in scalability. Tumor slice cultivation systems integrate

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biosensors and mechanical stimuli but require complex operations , while tumor cell
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invasion models facilitate high-throughput screening with minimal sample volumes ,
albeit with contamination risks. PDMS-based in vitro cell extravasation models

incorporate microvascular networks for real-time imaging but involve laborious chip

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fabrication . Sano et al. also mentioned High absorptivity of hydrophobic small-
molecule drugs, leading to significant alterations in effective drug concentration and

pharmacokinetic profiles. Key strengths of PDMS include high biomimicry for precise

microenvironment replication, excellent reproducibility 71 , and multifunctional

integration for real-time monitoring. Limitations include restricted utility for large

tissue specimens, time-consuming fabrication processes (e.g., photolithography), and
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contamination susceptibility during open operations . 3D printing technologies offer
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innovative solutions for tumor modeling. Gallegos-Martínez et al. and Rahimifard et
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al. developed devices for multicellular and hydrogel-embedded cultures, streamlining
prototyping and reducing costs, though SLA resin limitations (biocompatibility, optical

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transparency) were noted. Ong et al. highlighted the user- and eco-friendly nature of
3D printing for spheroid formation assessment. However, resolution limitations at the

cellular level, limited optical transparency and biocompatibility concern with certain

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materials remain critical challenges. Li et al. employed 3D bioprinting to create liver
cancer cell clusters, reducing preparation workload but facing precision issues requiring

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bioink perfusion. Moroni et al. stated that most extruded bioprints have a resolution
between 50-200 μm, while human capillaries are only 5-10 μm in diameter. This

directly leads to the fact that the bioprinted vascular network cannot truly mimic

physiological capillaries at scale, and can only produce large "vasculatures" rather than

real "capillaries". In summary, PDMS excels in precision and reproducibility but

struggles with scalability, while 3D printing offers rapid prototyping and reduced costs

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