Strategies to control cellular spatial organization in microphysiological systems

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Spatial organization is fundamental to tissue physiology, as it governs how cells migrate, grow, differentiate, and interact within their native environments. In living tissues, cells are positioned within finely tuned microarchitectures defined by chemical gradients, boundaries, and mechanical cues - features that are essential for proper tissue function and homeostasis. Microphysiological systems (MPSs) aim to replicate key aspects of human tissue in vitro, yet without appropriate spatial control, they often fail to reproduce certain aspects of tissue-level organization and function. In this review, we categorize spatial patterning strategies into two main approaches: direct methods, which involve the physical placement of cells or compartments using techniques such as 3D bioprinting, microfluidic compartmentalization, and physical trapping; and indirect methods, which rely on cellular responses to engineered environmental cues, including extracellular matrix (ECM) composition, mechanical gradients, and soluble factor distributions. While direct methods offer precision and reproducibility, indirect strategies more closely reflect natural developmental and self-organizing processes. We discuss how these approaches are applied across diverse biological structures, from cellular interfaces and barrier tissues to dynamic host-microbe systems. Enhancing spatial fidelity in MPSs is

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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