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Strategies to control cellular spatial organization in microphysiological systems.

Hung Dong Truong1, Zhixing Ge2, Elgene Chng2

  • 1Department of Biomedical Engineering, National University of Singapore, Singapore, 117583, Singapore. hung.truongbme@gmail.com.

Microsystems & Nanoengineering
|March 11, 2026
PubMed
Summary
This summary is machine-generated.

Spatial organization is crucial for tissue function. This review explores direct and indirect methods to control cell positioning in microphysiological systems (MPSs) for better disease modeling and drug screening.

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Area of Science:

  • Tissue engineering and regenerative medicine
  • Cell biology and biophysics
  • Microphysiological systems (MPSs) development

Background:

  • Tissue physiology relies on precise spatial organization of cells within microarchitectures.
  • Microphysiological systems (MPSs) aim to mimic human tissues but often lack spatial control, hindering accurate function replication.
  • Natural tissue development involves complex chemical and mechanical cues that guide cellular arrangement.

Purpose of the Study:

  • To review and categorize spatial patterning strategies for enhancing microphysiological systems (MPSs).
  • To highlight the importance of spatial fidelity in replicating tissue complexity in vitro.
  • To discuss applications in disease modeling, developmental biology, and drug screening.

Main Methods:

  • Categorization of spatial patterning into direct methods (e.g., 3D bioprinting, microfluidics) and indirect methods (e.g., ECM composition, mechanical gradients).
  • Analysis of techniques for physical placement of cells and compartments.
  • Examination of cellular responses to engineered environmental cues.

Main Results:

  • Direct methods offer precision and reproducibility in cell placement.
  • Indirect methods better mimic natural self-organizing processes.
  • Both approaches are applicable to diverse biological structures, including interfaces, barrier tissues, and host-microbe systems.

Conclusions:

  • Improving spatial fidelity in MPSs is essential for recapitulating complex tissue organization.
  • Enhanced spatial control in MPSs will significantly advance disease modeling and drug discovery.
  • Future research should focus on integrating direct and indirect spatial patterning strategies for more physiologically relevant models.