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devices and competition with conventional microfabrication techniques further hinder

their translation from laboratory research to commercial and clinical adoption. Beyond

current applications, we explore how integration with novel biosensing modalities and
computational analytics could revolutionize personalized cancer diagnostics and

treatment development.

3D-printed microfluidics demonstrate transformative potential in tumor research.

Building upon 3D printing, 4D printing introduces a temporal dimension through

stimulus-responsive systems activated by pressure, light, or heat, enabling dynamic

modulation of flow dynamics. The reversible shape-changing behavior of soft materials

enhances the flexibility and complexity of microfluidic actuator 149–151 . Utilizing shape-

memory polymers' (SMPs) phase-change capability to dynamically tune microchannel

geometries via thermal/optical stimuli 152 , next-generation tumor-on-chip models will

precisely mimic patient-specific biology and enable real-time drug delivery
optimization, advancing precision therapy.

However, 4D printing still faces considerable technical challenges, such as the

biocompatibility and long-term stability of SMPs, precise control over stimulus

application, and reproducible dynamic responses under physiological conditions 153 .

Moreover, clinical translation is hampered by significant hurdles including chip-to-

human physiological discrepancies, a lack of standardization in fabrication and

operational protocols, and the inherent complexity of integrating dynamic materials

into biomedical devices 154,155 .

Building on 3D/4D printing, Lai and Wang 156 conceptualized 5D printing:

embedded information (e.g., growth factors, nanoparticles, genetic/cellular data) as the

fifth dimension. 5D printing yields structures with shape-changing and information-
embedding capabilities that actively interact with their environment, unlike passive

3D/4D objects. 5D-printed scaffolds represent a transformative advancement in

biofabrication, integrating spatially encoded structural information with dynamic,

stimuli-responsive properties that actively interface with native biological

microenvironments. These sophisticated constructs achieve two paradigm-shifting
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