Cell-generated forces play a foundational role in tissue dynamics and homeostasis and are critically important in several biological processes, including cell migration, wound healing, morphogenesis, and cancer metastasis. Quantifying such forces in vivo is technically challenging and requires novel strategies that capture mechanical information across molecular, cellular, and tissue length scales, while allowing these studies to be performed in physiologically realistic biological models. Advanced biomaterials can be designed to non-destructively measure these stresses in vitro , and here, we review mechanical characterizations and force-sensing biomaterial-based technologies to provide insight into the mechanical nature of tissue processes. We specifically and uniquely focus on the use of these techniques to identify characteristics of cell and tissue “tensegrity:” the hierarchical and modular interplay between tension and compression that provide biological tissues with remarkable mechanical properties and behaviors. Based on these observed patterns, we highlight and discuss the emerging role of tensegrity at multiple length scales in tissue dynamics from homeostasis, to morphogenesis, to pathological dysfunction.

Organs-on-a-chip have emerged as next-generation tissue engineered models to accurately capture realistic human tissue behaviour, thereby addressing many of the challenges associated with using animal models in research. Mechanical features of the culture environment have emerged as being critically important in designing organs-on-a-chip, as they play important roles in both stimulating realistic tissue formation and function, as well as capturing integrative elements of homeostasis, tissue function, and tissue degeneration in response to external insult and injury. Despite the demonstrated impact of incorporating mechanical cues in these models, strategies to measure these mechanical tissue features in microfluidically-compatible formats directly on-chip are relatively limited. In this review, we first describe general microfluidically-compatible Organs-on-a-chip sensing strategies, and categorize these advances based on the specific advantages of incorporating them on-chip. We then consider foundational and recent advances in mechanical analysis techniques spanning cellular to tissue length scales; and discuss their integration into Organs-on-a-chips for more effective drug screening, disease modeling, and characterization of biological dynamics.

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