Robust and Precise Wounding and Analysis of Engineered Contractile Tissues

Dubois, Sarah J.; Kalashnikov, Nikita; Moraes, Christopher

doi:10.1089/ten.tec.2019.0123

Cited by 9 publications

(9 citation statements)

References 55 publications

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“…Moreover, the 3D patterned presentation of adhesive ligands may also affect mechanobiological function 63 . Finally, these fundamental mechanisms are likely co-regulated by other disease-related features, including soluble factors 17 , matrix composition 64 , membrane proteins such as syncytin 22 and more complex mechanical features of the substrate such as non-linear elasticity and viscoplasticity 65 ; suggesting the need for highly combinatorial studies of factors affecting this process.…”

Section: Discussionmentioning

confidence: 99%

Mechanobiological regulation of placental trophoblast fusion and function through extracellular matrix rigidity

Sagrillo-Fagundes

Mok

et al. 2020

Sci Rep

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the syncytiotrophoblast is a multinucleated layer that plays a critical role in regulating functions of the human placenta during pregnancy. Maintaining the syncytiotrophoblast layer relies on ongoing fusion of mononuclear cytotrophoblasts throughout pregnancy, and errors in this fusion process are associated with complications such as preeclampsia. While biochemical factors are known to drive fusion, the role of disease-specific extracellular biophysical cues remains undefined. Since substrate mechanics play a crucial role in several diseases, and preeclampsia is associated with placental stiffening, we hypothesize that trophoblast fusion is mechanically regulated by substrate stiffness. We developed stiffness-tunable polyacrylamide substrate formulations that match the linear elasticity of placental tissue in normal and disease conditions, and evaluated trophoblast morphology, fusion, and function on these surfaces. our results demonstrate that morphology, fusion, and hormone release is mechanically-regulated via myosin-ii; optimal on substrates that match healthy placental tissue stiffness; and dysregulated on disease-like and supraphysiologically-stiff substrates. We further demonstrate that stiff regions in heterogeneous substrates provide dominant physical cues that inhibit fusion, suggesting that even focal tissue stiffening limits widespread trophoblast fusion and tissue function. These results confirm that mechanical microenvironmental cues influence fusion in the placenta, provide critical information needed to engineer better in vitro models for placental disease, and may ultimately be used to develop novel mechanically-mediated therapeutic strategies to resolve fusion-related disorders during pregnancy. The human placental barrier is responsible for several critical functions during pregnancy including nutrient transport, gas exchange, waste elimination and hormone secretion 1. The placenta hence directly impacts fetal development 2 , immune tolerance 3 , and gestational length 4 , each of which can profoundly affect long-term quality of life and healthcare economics for both mother and baby 5-8. Transport across this fetal-maternal interface is regulated by the syncytiotrophoblast, a multinucleated layer that forms the outer surface of the placental villi 9. The syncytiotrophoblast arises and is maintained by continuous fusion of mononuclear villous cytotrophoblasts (vCTBs) 10 , through a tightly regulated process that can only be partially recreated in vitro 11. Disruption of fusion results in placental malformation and aberrant villous trophoblast turnover 10 , which is associated with life-altering pregnancy complications such as preeclampsia 12 and intrauterine growth restriction 13. Several biochemical factors are known to regulate placental trophoblast fusion in vitro and in vivo, including growth factors 14-16 , hormones 17 , proteases 18-20 , transcription factors 21 and membrane proteins 22. Despite this wealth of information, fusion remains a stochastic and poorly controlled process in cult...

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Section: Discussionmentioning

confidence: 99%

Mechanobiological regulation of placental trophoblast fusion and function through extracellular matrix rigidity

Sagrillo-Fagundes

Mok

et al. 2020

Sci Rep

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“…Not only is this coordination of forces and tissue prestress key during morphogenesis but also during wound healing to orchestrate collective cell migration 13 and initiate wound closure. 206 …”

Section: Emerging Views Of Tensegrity In Biologymentioning

confidence: 99%

Revisiting tissue tensegrity: Biomaterial-based approaches to measure forces across length scales

et al. 2021

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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.

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“…3 Thanks to these culture platforms, much has been uncovered about the biological effects of stiffness. 4 However, many living tissues such as skin, muscle, liver and brain inherently exhibit time-dependent energy-dissipative mechanical behavior 5,6 and viscoelasticity is now emerging as an important parameter in cell-matrix mechanobiological interactions. 6 Tunable viscoelastic hydrogel culture substrates are a useful tool to understand the biological significance of viscoelasticity.…”

Section: Introductionmentioning

confidence: 99%