Dynamic Hydrogels: Switching of 3D Microenvironments Using Two‐Component Naturally Derived Extracellular Matrices

Gillette, Brian M.; Jensen, Jacob A.; Wang, Meixin; Tchao, Jason; Sia, Samuel K.

doi:10.1002/adma.200902265

Cited by 152 publications

(142 citation statements)

References 34 publications

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“…Although many researchers have investigated collagen hydrogel network structure, no standard automated image analysis technique has yet emerged and therefore wide variation exists in published structural characteristics. Approaches in recent publications utilize algorithms exploiting a wide range of image segmentation and thresholding techniques, 12,21,26,27,34,41,44,47,49,64,76 grid-based estimation, 27,40,49 and even Fourier transforms and autocorrelation. 34,40,68 Further, manual estimation of dimensions of user-identified fibers and pores is not uncommon.…”

Section: Figmentioning

confidence: 99%

“…80 Fiber structure has often been measured in conjunction with other material properties, such as polymerization kinetics, 12,21,38,50,64,79 mechanical properties, 12,13,16,21,26,30,34,35,41,44,47,54,55,60,72,76 or diffusivity. 19,27,49,72 The goal of such experiments is usually development of predictive models that eliminate the need for time-consuming, expensive measurement of all relevant properties. However, because of the interdependence of hydrogel properties on fabrication parameters, such correlations have value only under limited conditions.…”

Section: Figmentioning

confidence: 99%

“…For further details on the method and analysis, see Seiffert and Oppermann. 95 The fluorescent probe used in FRAP measurements in collagen hydrogels is often an easily labeled model protein such as dextran 19,27,49,94 because it is available in a wide range of molecular weights and thus can be matched to a molecule of interest. Bioactive molecules in ECM range from small soluble cytokines and growth factors, with molecular weight on the order of 10 0 -10 1 kDa, 10,94,97,98 to large insoluble macromolecules, such as glycosaminoglycans (GAGs) and proteoglycans, with molecular weight on the order of 10 2 -10 3 kDa.…”

Section: Transportmentioning

confidence: 99%

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Review of Collagen I Hydrogels for Bioengineered Tissue Microenvironments: Characterization of Mechanics, Structure, and Transport

Antoine

Vlachos

Rylander³

2014

Tissue Engineering Part B: Reviews

480

353

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Type I collagen hydrogels have been used successfully as three-dimensional substrates for cell culture and have shown promise as scaffolds for engineered tissues and tumors. A critical step in the development of collagen hydrogels as viable tissue mimics is quantitative characterization of hydrogel properties and their correlation with fabrication parameters, which enables hydrogels to be tuned to match specific tissues or fulfill engineering requirements. A significant body of work has been devoted to characterization of collagen I hydrogels; however, due to the breadth of materials and techniques used for characterization, published data are often disjoint and hence their utility to the community is reduced. This review aims to determine the parameter space covered by existing data and identify key gaps in the literature so that future characterization and use of collagen I hydrogels for research can be most efficiently conducted. This review is divided into three sections: (1) relevant fabrication parameters are introduced and several of the most popular methods of controlling and regulating them are described, (2) hydrogel properties most relevant for tissue engineering are presented and discussed along with their characterization techniques, (3) the state of collagen I hydrogel characterization is recapitulated and future directions are proposed. Ultimately, this review can serve as a resource for selection of fabrication parameters and material characterization methodologies in order to increase the usefulness of future collagenhydrogel-based characterization studies and tissue engineering experiments.

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Section: Figmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Section: Transportmentioning

confidence: 99%

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Review of Collagen I Hydrogels for Bioengineered Tissue Microenvironments: Characterization of Mechanics, Structure, and Transport

Antoine

Vlachos

Rylander³

2014

Tissue Engineering Part B: Reviews

480

353

View full text Add to dashboard Cite

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“…There are only a few examples of systems where stiffness can be dynamically increased. Collagen-alginate composite hydrogels have been investigated, demonstrating mechanical properties altered by the introduction of divalent cations 73 . It is important to note that the introduction of calcium may also alter cell signalling.…”

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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“…For example, Gillette et al 23 reported collagen-alginate composite hydrogels, where mechanics are altered with the introduction of divalent cations, yet calcium may alter cell signalling, and the long-term stability of these gels is limited; external stimuli such as pH 24 and temperature 25,26 can be used to alter matrix stiffness, but only with large volumetric and hydrophobicity changes; free DNA was used to dynamically control the mechanics of DNA hybrid hydrogels 27 ; however, slow reaction kinetics (vary from 4 h to 1 day) [28][29][30] , homogeneity through the sample owing to retarded diffusion 31 , significant changes in the net charge of the hydrogel (free DNA is highly negatively charged) 30,31 , lack of information on long-term (>7 days) stability of the gels in culture condition, and possible problems with cellular compatibility (the similarity of the DNA sequence to the genome of the specific cell type used) 28,32 are some of their limitations.…”

mentioning

confidence: 99%

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

2012

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Biological processes are dynamic in nature, and growing evidence suggests that matrix stiffening is particularly decisive during development, wound healing and disease; yet, nearly all in vitro models are static. Here we introduce a step-wise approach, addition then lightmediated crosslinking, to fabricate hydrogels that stiffen (for example, ~3-30 kPa) in the presence of cells, and investigated the short-term (minutes-to-hours) and long-term (daysto-weeks) cell response to dynamic stiffening. When substrates are stiffened, adhered human mesenchymal stem cells increase their area from ~500 to 3,000 µm 2 and exhibit greater traction from ~1 to 10 kPa over a timescale of hours. For longer cultures up to 14 days, human mesenchymal stem cells selectively differentiate based on the period of culture, before or after stiffening, such that adipogenic differentiation is favoured for later stiffening, whereas osteogenic differentiation is favoured for earlier stiffening.

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Dynamic Hydrogels: Switching of 3D Microenvironments Using Two‐Component Naturally Derived Extracellular Matrices

Cited by 152 publications

References 34 publications

Review of Collagen I Hydrogels for Bioengineered Tissue Microenvironments: Characterization of Mechanics, Structure, and Transport

Review of Collagen I Hydrogels for Bioengineered Tissue Microenvironments: Characterization of Mechanics, Structure, and Transport

Moving from static to dynamic complexity in hydrogel design

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

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