Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics

Guvendiren, Murat; Burdick, Jason A.

doi:10.1038/ncomms1792

Cited by 593 publications

(578 citation statements)

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“…4). This was recently used to probe the timing of mechanical changes on mesenchymal stem cell fate 77 . As a final example, the kinetics of gelation (crosslinking of thiolated hyaluronic acid with PEG diacrylate, Fig.…”

Section: Triggered Changes In Hydrogel Propertiesmentioning

confidence: 99%

Moving from static to dynamic complexity in hydrogel design

2012

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Hydrogels are water-swollen polymer networks that have found a range of applications from biological scaffolds to contact lenses. Historically, their design has consisted primarily of static systems and those that exhibit simple degradation. However, advances in polymer synthesis and processing have led to a new generation of dynamic systems that are capable of responding to artificial triggers and biological signals with spatial precision. These systems will open up new possibilities for the use of hydrogels as model biological structures and in tissue regeneration.H ydrogels are water-swollen polymer networks that have been used for many decades, with applications as varied as contact lenses and super-absorbant materials. As the field of biomedical engineering has developed, hydrogels have become a prime candidate for application as molecule delivery vehicles and as carriers for cells in tissue engineering, owing to their ability to mimic many aspects of the native cellular environment (for example, high water content, mechanical properties that match soft tissues). Traditional hydrogels, formed through the covalent and non-covalent crosslinking of polymer chains, were regarded as relatively inert materials, providing a simple biomimetic three-dimensional (3D) environment, either for tissue production by local resident cells or for positioning of cells delivered in vivo. However, the simplicity of these materials may have in fact hindered their application, restricting cellular interactions with the environment and preventing uniform extracellular matrix (ECM) production and proper tissue development. In addition, these materials were limited to modelling static environments and lacked the spatiotemporal dynamic properties relevant for complex tissue processes. Fortunately, during the last decade the concepts of hydrogel design and cellular interaction have evolved, shedding light on how they may control cell behaviour, particularly for tissue engineering applications.Hydrogels with a range of mechanical properties, and capable of incorporating a wide range of biologically relevant molecules, from individual functional groups to multidomain proteins, are currently in development 1 . In addition, hydrogels are being designed with spatial heterogeneity, to either replicate properties in native tissue structures or to produce constructs with distinct regionally specific cell behavior 2 . As a result, studies to date have clearly demonstrated the possibility of creating well-defined microenvironments with control over the 3D presentation of signals to cells 3 . However, recently there has been a focus on the concept of hydrogels that exhibit dynamic complexity. These materials should evolve with time and in response to

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Section: Triggered Changes In Hydrogel Propertiesmentioning

confidence: 99%

Moving from static to dynamic complexity in hydrogel design

2012

Self Cite

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“…While these studies demonstrated the MMT's utility as an mechanobiological diagnostic system, for many mechanosensitive cell types, such as cardiomyocytes and osteocytes, it has been shown that they require relatively long culture periods (weeks) to interact with the surrounding mechanical environment and to reach maturity. 20 Therefore, if the MMT system is to be used as a research tool that can accommodate various mechano-sensitive cell types, its long-term culture capacity needs to be evaluated.…”

Section: Introductionmentioning

confidence: 99%

Magnetic approaches to study collective three-dimensional cell mechanics in long-term cultures (invited)

Zhao

Boudou

Wang

et al. 2014

Journal of Applied Physics

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Contractile forces generated by cells and the stiffness of the surrounding extracellular matrix are two central mechanical factors that regulate cell function. To characterize the dynamic evolution of these two mechanical parameters during tissue morphogenesis, we developed a magnetically actuated micro-mechanical testing system in which fibroblast-populated collagen microtissues formed spontaneously in arrays of microwells that each contains a pair of elastomeric microcantilevers. We characterized the magnetic actuation performance of this system and evaluated its capacity to support long-term cell culture. We showed that cells in the microtissues remained viable during prolonged culture periods of up to 15 days, and that the mechanical properties of the microtissues reached and maintained at a stable state after a fast initial increase stage. Together, these findings demonstrate the utility of this microfabricated bio-magneto-mechanical system in extended mechanobiological studies in a physiologically relevant 3D environment. V C 2014 AIP Publishing LLC.

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“…Guvendiren and Burdick showed that the kinetics of light-mediated stiffening (≈3-30 kPa) of HA substrates modulated MSC differentiation. [94] MSCs differentiated into osteoblasts (adipocytes) when stiffening took place within hours (within days-to-weeks) time, maximizing (minimizing) the time cells were on stiff substrates. Stiffening HA substrates were used to mimic fibrosis and consequent myofibroblast activation in hepatic stellate cells.…”

Section: Time-dependent Matrix Stiffeningmentioning

confidence: 99%

Mechanotransduction and Growth Factor Signalling to Engineer Cellular Microenvironments

Cipitria

Salmerón-Sánchez

2017

Adv Healthcare Materials

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Engineering cellular microenvironments involves biochemical factors, the extracellular matrix (ECM) and the interaction with neighbouring cells. This progress report provides a critical overview of key studies that incorporate growth factor (GF) signalling and mechanotransduction into the design of advanced microenvironments. Materials systems have been developed for surface‐bound presentation of GFs, either covalently tethered or sequestered through physico‐chemical affinity to the matrix, as an alternative to soluble GFs. Furthermore, some materials contain both GF and integrin binding regions and thereby enable synergistic signalling between the two. Mechanotransduction refers to the ability of the cells to sense physical properties of the ECM and to transduce them into biochemical signals. Various aspects of the physics of the ECM, i.e. stiffness, geometry and ligand spacing, as well as time‐dependent properties, such as matrix stiffening, degradability, viscoelasticity, surface mobility as well as spatial patterns and gradients of physical cues are discussed. To conclude, various examples illustrate the potential for cooperative signalling of growth factors and the physical properties of the microenvironment for potential applications in regenerative medicine, cancer research and drug testing.

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Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics

Cited by 593 publications

References 57 publications

Moving from static to dynamic complexity in hydrogel design

Moving from static to dynamic complexity in hydrogel design

Magnetic approaches to study collective three-dimensional cell mechanics in long-term cultures (invited)

Mechanotransduction and Growth Factor Signalling to Engineer Cellular Microenvironments

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