Fluid Mechanics as a Driver of Tissue-Scale Mechanical Signaling in Organogenesis

Gilbert, Rachel M.; Morgan, Joshua T.; Marcin, Elizabeth; Gleghorn, Jason P.

doi:10.1007/s40139-016-0117-3

Cited by 13 publications

(9 citation statements)

References 101 publications

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“…A variety of tissues and organs use fluid flow in networks to sense the mechanical environment, thereby contributing to their morphogenesis, active maintenance, and adaptation to changing demands ( 1 ). Important examples include the formation of the circulation and nervous system ( 2 , 3 ), both the rapid and long-term adaptation of the lungs ( 4 ), and the adaptation of bone to mechanical loads ( 5 – 7 ). Important distinguishing characteristics between networks are the mechanical flexibility of the walls of their channels and their network architecture.…”

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confidence: 99%

The mechanoresponse of bone is closely related to the osteocyte lacunocanalicular network architecture

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Schemenz

Wagermaier

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Organisms rely on mechanosensing mechanisms to adapt to changes in their mechanical environment. Fluid-filled network structures not only ensure efficient transport but can also be employed for mechanosensation. The lacunocanalicular network (LCN) is a fluid-filled network structure, which pervades our bones and accommodates a cell network of osteocytes. For the mechanism of mechanosensation, it was hypothesized that load-induced fluid flow results in forces that can be sensed by the cells. We use a controlled in vivo loading experiment on murine tibiae to test this hypothesis, whereby the mechanoresponse was quantified experimentally by in vivo micro-computed tomography (µCT) in terms of formed and resorbed bone volume. By imaging the LCN using confocal microscopy in bone volumes covering the entire cross-section of mouse tibiae and by calculating the fluid flow in the three-dimensional (3D) network, we could perform a direct comparison between predictions based on fluid flow velocity and the experimentally measured mechanoresponse. While local strain distributions estimated by finite-element analysis incorrectly predicts preferred bone formation on the periosteal surface, we demonstrate that additional consideration of the LCN architecture not only corrects this erroneous bias in the prediction but also explains observed differences in the mechanosensitivity between the three investigated mice. We also identified the presence of vascular channels as an important mechanism to locally reduce fluid flow. Flow velocities increased for a convergent network structure where all of the flow is channeled into fewer canaliculi. We conclude that, besides mechanical loading, LCN architecture should be considered as a key determinant of bone adaptation.

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confidence: 99%

The mechanoresponse of bone is closely related to the osteocyte lacunocanalicular network architecture

Tol

Schemenz

Wagermaier

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…This cellular mechanotransduction pathway contributes to airway epithelial tree growth ( 19 , 20 ), alveolar cell differentiation ( 16 ), and thus, surfactant production. As gestation progresses, this fluid leaves the lung via the larynx and either enters the amniotic fluid or is swallowed by the fetus ( 21 , 22 ).…”

Section: Fluid Pressure In Pulmonary Development and The Inception Of...mentioning

confidence: 99%

The Cellular and Molecular Effects of Fetoscopic Endoluminal Tracheal Occlusion in Congenital Diaphragmatic Hernia

et al. 2022

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Congenital diaphragmatic hernia (CDH) is a complex disease associated with pulmonary hypoplasia and pulmonary hypertension. Great strides have been made in our ability to care for CDH patients, specifically in the prenatal improvement of lung volume and morphology with fetoscopic endoluminal tracheal occlusion (FETO). While the anatomic effects of FETO have been described in-depth, the changes it induces at the cellular and molecular level remain a budding area of CDH research. This review will delve into the cellular and molecular effects of FETO in the developing lung, emphasize areas in which further research may improve our understanding of CDH, and highlight opportunities to optimize the FETO procedure for improved postnatal outcomes.

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“…While these platforms are highly complex and challenging to develop, there is a corresponding increase in control and ability to separate spatiotemporal responses, with less sacrifice of physiologic conditions. These models are common for studying organ development 91 , 165 , 168 , 200 and bioreactors for organ and lung conditioning for transplant, 96 , 188 but less common with applications to studying disease pathophysiology. This is especially critical in studying SARS-CoV-2 pathology and the progression of COVID-19.…”

Section: Opportunities For Bioengineers To Study Respiratory Viral LImentioning

confidence: 99%

Significant Unresolved Questions and Opportunities for Bioengineering in Understanding and Treating COVID-19 Disease Progression

et al. 2020

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COVID-19 is a disease that manifests itself in a multitude of ways across a wide range of tissues. Many factors are involved, and though impressive strides have been made in studying this novel disease in a very short time, there is still a great deal that is unknown about how the virus functions. Clinical data has been crucial for providing information on COVID-19 progression and determining risk factors. However, the mechanisms leading to the multi-tissue pathology are yet to be fully established. Although insights from SARS-CoV-1 and MERS-CoV have been valuable, it is clear that SARS-CoV-2 is different and merits its own extensive studies. In this review, we highlight unresolved questions surrounding this virus including the temporal immune dynamics, infection of non-pulmonary tissue, early life exposure, and the role of circadian rhythms. Risk factors such as sex and exposure to pollutants are also explored followed by a discussion of ways in which bioengineering approaches can be employed to help understand COVID-19. The use of sophisticated in vitro models can be employed to interrogate intercellular interactions and also to tease apart effects of the virus itself from the resulting immune response. Additionally, spatiotemporal information can be gleaned from these models to learn more about the dynamics of the virus and COVID-19 progression. Application of advanced tissue and organ system models into COVID-19 research can result in more nuanced insight into the mechanisms underlying this condition and elucidate strategies to combat its effects.

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Fluid Mechanics as a Driver of Tissue-Scale Mechanical Signaling in Organogenesis

Cited by 13 publications

References 101 publications

The mechanoresponse of bone is closely related to the osteocyte lacunocanalicular network architecture

The mechanoresponse of bone is closely related to the osteocyte lacunocanalicular network architecture

The Cellular and Molecular Effects of Fetoscopic Endoluminal Tracheal Occlusion in Congenital Diaphragmatic Hernia

Significant Unresolved Questions and Opportunities for Bioengineering in Understanding and Treating COVID-19 Disease Progression

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