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Tissues grow and remodel in response to mechanical cues, extracellular and intracellular signals experienced through various biological events, from the developing embryo to disease and aging. The macroscale response of soft tissues is typically nonlinear, viscoelastic anisotropic, and often emerges from the hierarchical structure of tissues, primarily their biopolymer fiber networks at the microscale. The adaptation to mechanical cues is likewise a multiscale phenomenon. Cell mechanobiology, the ability of cells to transform mechanical inputs into chemical signaling inside the cell, and subsequent regulation of cellular behavior through intra- and inter-cellular signaling networks, is the key coupling at the microscale between the mechanical cues and the mechanical adaptation seen macroscopically. To fully understand mechanics of tissues in growth and remodeling as observed at the tissue level, multiscale models of tissue mechanobiology are essential. In this review, we summarize the state-of-the art modeling tools of soft tissues at both scales, the tissue level response, and the cell scale mechanobiology models. To help the interested reader become more familiar with these modeling frameworks, we also show representative examples. Our aim here is to bring together scientists from different disciplines and enable the future leap in multiscale modeling of tissue mechanobiology.
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Key developments that impacted the field of mechanobiology and mechanotransduction: MECHANOBIOLOGY AND SIGNAL TRANSDUCTION
Advances in mechanobiology have evolved through insights from multiple disciplines including structural engineering, biomechanics, vascular biology, and orthopaedics. In this paper, we reviewed the impact of key reports related to the study of applied loads on tissues and cells and the resulting signal transduction pathways. We addressed how technology has helped advance the burgeoning field of mechanobiology (over 33,600 publications from 1970 to 2016). We analyzed the impact of critical ideas and then determined how these concepts influenced the mechanobiology field by looking at the citation frequency of these reports as well as tracking how the overall number of citations within the field changed over time. These data allowed us to understand how a key publication, idea, or technology guided or enabled the field. Initial observations of how forces acted on bone and soft tissues stimulated the development of computational solutions defining how forces affect tissue modeling and remodeling. Enabling technologies, such as cell and tissue stretching, compression, and shear stress devices, allowed more researchers to explore how deformation and fluid flow affect cells. Observation of the cell as a tensegrity structure and advanced methods to study genetic regulation in cells further advanced knowledge of specific mechanisms of mechanotransduction. The future of the field will involve developing gene and drug therapies to simulate or augment beneficial load regimens in patients and in mechanically conditioning organs for implantation. Here, we addressed a history of the field, but we limited our discussions to advances in musculoskeletal mechanobiology, primarily in bone, tendon, and ligament tissues.
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- Award ID(s):
- 1702841
- PAR ID:
- 10067137
- Date Published:
- Journal Name:
- Journal of Orthopaedic Research
- ISSN:
- 0736-0266
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1002/jor.23707
