Calcium Signaling Regulates Valvular Interstitial Cell Alignment and Myofibroblast Activation in Fast‐Relaxing Boronate Hydrogels

Ma, Hao; Macdougall, Laura J.; Gonzalez-Rodriguez, Andrea; Schroeder, Megan E.; Batan, Dilara; Weiß, Robert M.; Anseth, Kristi S.

doi:10.1002/mabi.202000268

Cited by 21 publications

(20 citation statements)

References 60 publications

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“…Adapted with permission. [ 158 ] Copyright 2020, Wiley‐VCH GmbH. c) Stitched, self‐healed hydrogel blocks containing different cell types showed migration of cells across the interface in boronate ester crosslinked hydrogels, indicating that the microenvironment is conducive for cell motility.…”

Section: Case Studies Of 3d Cell Culture In DCC Hydrogelsmentioning

confidence: 99%

“…[ 100 ] Similarly, a 90% stress relaxation hydrogel comprised of 40% SPAAC and 60% BE crosslinks allowed extensive spreading of valvular interstitial cells, promoted cellular assembly into aligned structures, increased the expression of a myofibroblast marker, and induced a high ratio of YAP/TAZ in the nucleus versus cytoplasm, thereby engaging the mechanotransduction pathway ( Figure a,b). [ 158 ]…”

Section: Case Studies Of 3d Cell Culture In DCC Hydrogelsmentioning

confidence: 99%

“…Adapted with permission. [ 158 ] Copyright 2020, Wiley‐VCH GmbH. b) Representative immunostaining images of nuclei (blue), F‐actin (orange), and α SMA stress fibers (green) of valvular interstitial cells cultured in different viscoelastic hydrogel formulations at day 5.…”

Section: Case Studies Of 3d Cell Culture In DCC Hydrogelsmentioning

confidence: 99%

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Designing Hydrogels for 3D Cell Culture Using Dynamic Covalent Crosslinking

Rizwan

Baker

Shoichet

2021

Adv Healthcare Materials

109

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Designing simple biomaterials to replicate the biochemical and mechanical properties of tissues is an ongoing challenge in tissue engineering. For several decades, new biomaterials have been engineered using cytocompatible chemical reactions and spontaneous ligations via click chemistries to generate scaffolds and water swollen polymer networks, known as hydrogels, with tunable properties. However, most of these materials are static in nature, providing only macroscopic tunability of the scaffold mechanics, and do not reflect the dynamic environment of natural extracellular microenvironment. For more complex applications such as organoids or co‐culture systems, there remain opportunities to investigate cells that locally remodel and change the physicochemical properties within the matrices. In this review, advanced biomaterials where dynamic covalent chemistry is used to produce stable 3D cell culture models and high‐resolution constructs for both in vitro and in vivo applications, are discussed. The implications of dynamic covalent chemistry on viscoelastic properties of in vitro models are summarized, case studies in 3D cell culture are critically analyzed, and opportunities to further improve the performance of biomaterials for 3D tissue engineering are discussed.

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Section: Case Studies Of 3d Cell Culture In DCC Hydrogelsmentioning

confidence: 99%

Section: Case Studies Of 3d Cell Culture In DCC Hydrogelsmentioning

confidence: 99%

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Designing Hydrogels for 3D Cell Culture Using Dynamic Covalent Crosslinking

Rizwan

Baker

Shoichet

2021

Adv Healthcare Materials

109

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Section: Mechanosensing In 3d Hydrogelsmentioning

confidence: 99%

Mechanics of 3D Cell–Hydrogel Interactions: Experiments, Models, and Mechanisms

et al. 2021

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Hydrogels are highly water-swollen molecular networks that are ideal platforms to create tissue mimetics owing to their vast and tunable properties. As such, hydrogels are promising cell-delivery vehicles for applications in tissue engineering and have also emerged as an important base for ex vivo models to study healthy and pathophysiological events in a carefully controlled three-dimensional environment. Cells are readily encapsulated in hydrogels resulting in a plethora of biochemical and mechanical communication mechanisms, which recapitulates the natural cell and extracellular matrix interaction in tissues. These interactions are complex, with multiple events that are invariably coupled and spanning multiple length and time scales. To study and identify the underlying mechanisms involved, an integrated experimental and computational approach is ideally needed. This review discusses the state of our knowledge on cell−hydrogel interactions, with a focus on mechanics and transport, and in this context, highlights recent advancements in experiments, mathematical and computational modeling. The review begins with a background on the thermodynamics and physics fundamentals that govern hydrogel mechanics and transport. The review focuses on two main classes of hydrogels, described as semiflexible polymer networks that represent physically cross-linked fibrous hydrogels and flexible polymer networks representing the chemically cross-linked synthetic and natural hydrogels. In this review, we highlight five main cell− hydrogel interactions that involve key cellular functions related to communication, mechanosensing, migration, growth, and tissue deposition and elaboration. For each of these cellular functions, recent experiments and the most up to date modeling strategies are discussed and then followed by a summary of how to tune hydrogel properties to achieve a desired functional cellular outcome. We conclude with a summary linking these advancements and make the case for the need to integrate experiments and modeling to advance our fundamental understanding of cell−matrix interactions that will ultimately help identify new therapeutic approaches and enable successful tissue engineering.

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“…Changing the elastic modulus of a viscoelastic matrix often also changes the loss modulus, making it impossible to disentangle viscous from elastic effects. Nonetheless, a number of studies based on static hydrogels with equal elastic, but different loss moduli, highlight the importance of viscoelasticity for tuning mechano-adaptation in FB (Chaudhuri et al 2015;Lou et al 2018;Ma et al 2020). To date, there is no system that allows one to dynamically tune one or the other property independently in the presence of cells.…”

Section: Hydrogels With Dynamically Tunable Stiffnessmentioning

confidence: 99%

Passive myocardial mechanical properties: meaning, measurement, models

et al. 2021

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Passive mechanical tissue properties are major determinants of myocardial contraction and relaxation and, thus, shape cardiac function. Tightly regulated, dynamically adapting throughout life, and affecting a host of cellular functions, passive tissue mechanics also contribute to cardiac dysfunction. Development of treatments and early identification of diseases requires better spatio-temporal characterisation of tissue mechanical properties and their underlying mechanisms. With this understanding, key regulators may be identified, providing pathways with potential to control and limit pathological development. Methodologies and models used to assess and mimic tissue mechanical properties are diverse, and available data are in part mutually contradictory. In this review, we define important concepts useful for characterising passive mechanical tissue properties, and compare a variety of in vitro and in vivo techniques that allow one to assess tissue mechanics. We give definitions of key terms, and summarise insight into determinants of myocardial stiffness in situ. We then provide an overview of common experimental models utilised to assess the role of environmental stiffness and composition, and its effects on cardiac cell and tissue function. Finally, promising future directions are outlined.

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Calcium Signaling Regulates Valvular Interstitial Cell Alignment and Myofibroblast Activation in Fast‐Relaxing Boronate Hydrogels

Cited by 21 publications

References 60 publications

Designing Hydrogels for 3D Cell Culture Using Dynamic Covalent Crosslinking

Designing Hydrogels for 3D Cell Culture Using Dynamic Covalent Crosslinking

Mechanics of 3D Cell–Hydrogel Interactions: Experiments, Models, and Mechanisms

Passive myocardial mechanical properties: meaning, measurement, models

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