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but faces material-related limitations. In clinical practice and scientific research, we

recommend: (1) For studying nanoparticle transport and vascular permeability: PDMS-

based devices are recommended, as they currently offer superior optical clarity for real-
time imaging, despite inherent drug absorption issues. (2) For generating patient-

specific avascular tumor models for high-throughput drug screening: 3D-bioprinted

spheroid/organoid arrays present an ideal solution. (3) For constructing integrated

multi-tissue models with perfusable vasculature: a hybrid approach utilizing high-

resolution 3D-printed molds for PDMS device fabrication currently represents the most

viable strategy.

4.1 Precision Drug Screening Using Microfluidic Device Arrays

3D tumor models overcome monolayer limitations by facilitating spatially

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relevant cell-cell and cell-matrix interactions . Tumor spheroids, well-characterized
early-stage cancer models, are widely used in research and drug development for

simplicity and structural similarity to in vivo conditions. Constructed from cancer cells

alone or co-cultured with stromal cells (scaffolded or scaffold-free), microfluidics

simulates tumor tissue/organs via in vitro models and spheroid culture systems,

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establishing drug screening platforms .

(1) Microfluidic Modeling of the TME

Researchers have developed microfluidic 3D tumor models with organ-specific

characteristics or varying tumor progression by controlling extracellular matrix
properties and cellular compositions for applications such as drug screening (Figure

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4A) . Furthermore, microfluidic devices have been demonstrated to effectively deliver
nutrients and/or drugs to tumor tissues through microchannels, thereby sustaining their

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physiological activities (Figure 4B) .The TME comprises heterogeneous ECM
components, neighboring cells (fibroblasts, pericytes, astrocytes), immune cells,

adipocytes, stem cells, vasculature, lymphatics, and physical conditions governing

convection/diffusion 94,95 . Introducing TME components into microfluidic devices

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