Cell Interactions with Biomaterials Gradients and Arrays

Simon, Carl G.; Yang, Yanyin; Thomas, Vinoy; Dorsey, Shauna M.; Morgan, Abby W.

doi:10.2174/138620709788681961

Cited by 23 publications

(25 citation statements)

References 117 publications

(253 reference statements)

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“…This has led to an abundance of data showing that various micro-environmental cues lead to differences in cell behaviors of interest. 1,24,30,33 The key question we seek to answer here is: how? How do these variations in micro-environment cause Cell biology literature includes many studies linking a particular integrin or signaling pathway with various cell behaviors so this may seem to be an answered question; however, existing information cannot explain how subtle differences in substrate (e.g., collagen I vs. collagen IV) can lead to differences in signaling.…”

Section: Discussionmentioning

confidence: 99%

Substrates Elicit Different Patterns of Intracellular Signaling Which in Turn Cause Differences in Cell Adhesion

2010

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Although intracellular signal transduction is relatively well understood, how the cells can distinguish among thousands of micro-environments is not. This study proposes that a systems level view of intracellular signaling is necessary to interpret differences in cell interactions with different substrates. Human umbilical vein endothelial cells were exposed to 10 substrates (9 adsorbed extracellular matrix proteins and uncoated polystyrene), and the activities of 4 intracellular signaling kinases were quantified for cells on each substrate as a function of time. Principal component analysis demonstrates that each substrate elicits a different pattern of signaling. Mean activity of the 4 kinases can distinguish 44 of 45 possible pair-wise comparisons among the substrates. Partial Least Squares Regression Analysis is used to hypothesize causal relationships between signaling activity and cell adhesion or b 1 -integrin expression. Inhibition studies generally confirm that ERK (extracellular signalrelated kinase) and JNK (c-Jun N-terminal kinase) cause increased adhesion and b 1 -integrin expression. Inhibition of IKK (IjB kinase), on the other hand, showed no statistically significant effect on b 1 -integrin expression and led to significant decreases in cell adhesion-confirming a causal link but opposite of the hypothesized relationship (that inhibition of IKK would increase adhesion).

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Section: Discussionmentioning

confidence: 99%

Substrates Elicit Different Patterns of Intracellular Signaling Which in Turn Cause Differences in Cell Adhesion

2010

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“…Such cell-material interactions will be critical in tissue engineering and can be leveraged to maximize tissue regeneration. CHT platforms offer a route to systematically investigate cell-material interactions to identify optimal material properties [3]. Here we described a method to fabricate continuous gradients hydrogel scaffolds that enable screening of cellular response to a wide range of scaffold properties within a single specimen.…”

Section: Resultsmentioning

confidence: 99%

“…Towards this goal, combinatorial and highthroughput (CHT) methods successfully utilized by the pharmaceutical industry for drug discovery [2] are being adapted in tissue engineering research [3]. CHT platforms can be used to systematically screen cell-material interactions and identify optimal scaffold properties to maximize desired tissue regeneration.…”

Section: Introductionmentioning

confidence: 99%

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Fabricating Gradient Hydrogel Scaffolds for 3D Cell Culture

Chatterjee¹,

Young²,

Simon³

2011

CCHTS

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Optimizing cell-material interactions is critical for maximizing regeneration in tissue engineering. Combinatorial and high-throughput (CHT) methods can be used to systematically screen tissue scaffolds to identify optimal biomaterial properties. Previous CHT platforms in tissue engineering have involved a two-dimensional (2D) cell culture format where cells were cultured on material surfaces. However, these platforms are inadequate to predict cellular response in a threedimensional (3D) tissue scaffold. We have developed a simple CHT platform to screen cellmaterial interactions in 3D culture format that can be applied to screen hydrogel scaffolds. Herein we provide detailed instructions on a method to prepare gradients in elastic modulus of photopolymerizable hydrogels.

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“…Thus, the development of a strategy that permits systematic and rapid screening of cell–scaffold interactions, particularly for a scaffold system with a broad range of properties, is critical. Combinatorial strategies have mainly been limited to two-dimensional (2D) culture in which arrays of isolated, individual scaffolds are rapidly produced and cells cultured on the surfaces [21–23]. However, three-dimensional (3D) culture is preferred as it better resembles the native tissue environment [24–26].…”

Section: Introductionmentioning

confidence: 99%

Continuous gradient scaffolds for rapid screening of cell–material interactions and interfacial tissue regeneration

2013

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In tissue engineering, the physical and chemical properties of the scaffold mediates cell behavior including regeneration. Thus, a strategy that permits rapid screening of cell-scaffold interactions is critical. Herein, we have prepared eight “hybrid” hydrogel scaffolds in the form of continuous gradients such that a single scaffold contains spatially varied properties. These scaffolds are based on combining an inorganic macromer [methacrylated star polydimethylsiloxane, PDMSstar-MA] and organic macromer [poly(ethylene glycol)diacrylate, PEG-DA] as well both aqueous and organic fabrication solvents. Having previously demonstrated its bioactivity and osteoinductivity, PDMSstar-MA is a particularly powerful component to incorporate into instructive gradient scaffolds based on PEG-DA. The following parameters were varied to produce the different gradients or gradual transitions in: (1) the wt% ratio of PDMSstar-MA to PEG-DA macromers, (2) the total wt% macromer concentration, (3) the number average molecular weight (Mn) of PEG-DA and (4) the Mn of PDMSstar-MA. Upon dividing each scaffold into four “zones” perpendicular to the gradient, we were able to demonstrate the spatial variation in morphology, bioactivity, swelling and modulus. Among these gradient scaffolds are those in which swelling and modulus are conveniently decoupled. In addition to rapid screening of cell-material interactions, these scaffolds are well-suited for regeneration of interfacial tissues (e.g. osteochondral tissues) that transition from one tissue type to another.

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Cell Interactions with Biomaterials Gradients and Arrays

Cited by 23 publications

References 117 publications

Substrates Elicit Different Patterns of Intracellular Signaling Which in Turn Cause Differences in Cell Adhesion

Substrates Elicit Different Patterns of Intracellular Signaling Which in Turn Cause Differences in Cell Adhesion

Fabricating Gradient Hydrogel Scaffolds for 3D Cell Culture

Continuous gradient scaffolds for rapid screening of cell–material interactions and interfacial tissue regeneration

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