Convergence of microengineering and cellular self-organization towards functional tissue manufacturing

Laurent, Jérémie; Blin, Guillaume; Chatelain, François; Vanneaux, Valérie; Fuchs, Alexandra; Larghero, Jérôme; Théry, Manuel

doi:10.1038/s41551-017-0166-x

Cited by 105 publications

(102 citation statements)

References 260 publications

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“…A three-dimensional (3D) cell culture confers a high degree of clinical and biological relevance to in vitro models [1][2][3][4][5]. Compared with conventional two-dimensional (2D) cell cultures, 3D cell cultures allow the cellular self-organization of appropriate extracellular matrix (ECM) assembly with complex cell-matrix and cell-cell interactions that mimic the functional properties of the corresponding tissue in vivo [6][7][8][9][10][11]. To realize the desired 3D cellular processes, numerous 3D biomimetic scaffolds that incorporate different biochemical, mechanical, or architectural cues have been developed for cell cultures [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Responsive Inverse Opal Scaffolds with Biomimetic Enrichment Capability for Cell Culture

et al. 2019

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Three-dimensional (3D) porous scaffolds have a demonstrated value for tissue engineering and regenerative medicine. Inspired by the predation processes of marine predators in nature, we present new photocontrolled shrinkable inverse opal graphene oxide (GO) hydrogel scaffolds for cell enrichment and 3D culture. The scaffolds with adjustable pore sizes and morphologies were created using a GO and N-isopropylacrylamide dispersed solution as a continuous phase of microfluidic emulsions for polymerizing and replicating. Because of the interconnected porous structures and the remotely controllable volume responsiveness of the scaffolds, the suspended cells could be enriched into the inner spaces of the scaffolds through predator-like swallowing and discharging processes. Hepatocyte cells concentrated in the scaffold pores could form denser 3D spheroids more quickly via the controlled compression force caused by the shrinking of the dynamic scaffolds. More importantly, with a program of scaffold enrichment with different cells, an unprecedented 3D multilayer coculture system of endothelial-cell-encapsulated hepatocytes and fibroblasts could be generated for applications such as liver-on-a-chip and bioartificial liver. It was demonstrated that the resultant multicellular system offered significant improvements in hepatic functions, such as albumin secretion, urea synthesis, and cytochrome P450 expression. These features of our scaffolds make them highly promising for the biomimetic construction of various physiological and pathophysiological 3D tissue models, which could be used for understanding tissue level biology and in vitro drug testing applications.

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Section: Introductionmentioning

confidence: 99%

Responsive Inverse Opal Scaffolds with Biomimetic Enrichment Capability for Cell Culture

et al. 2019

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“…Therefore to identify the key elementary processes regulating cell behaviors, a trade-off has to be made between tissue-like morphological mimicry and focused biophysical investigation. Micro-engineering of cell-culture devices now offer the possibility to impose defined spatial boundary conditions at the multi-cellular, cellular or sub-cellular level, which can recapitulate specific geometrical and physical constraints cells are submitted to in vivo (Laurent et al, 2017;Théry, 2010).…”

Section: Introductionmentioning

confidence: 99%

Biophysical properties of intermediate states of EMT outperform both epithelial and mesenchymal states

Margaron

Nagai

Guyon

et al. 2019

Preprint

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Potential metastatic cells can dissociate from a primary breast tumor by undergoing an epithelial-to-mesenchymal transmission (EMT). Recent work has revealed that cells in intermediate states of EMT acquire an augmented capacity for tumor-cell dissemination. These states have been characterized by molecular markers, but the structural features and the cellular mechanisms that underlie the acquisition of their invasive properties are still unknown. Using human mammary epithelial cells, we generated cells in intermediate states of EMT through the induction of a single EMT-inducing transcription factor, ZEB1, and cells in a mesenchymal state by stimulation with TGFβ. In stereotypic and spatially-defined culture conditions, the architecture, internal organization and mechanical properties of cells in the epithelial, intermediate and mesenchymal state were measured and compared. We found that the lack of intercellular cohesiveness in epithelial and mesenchymal cells can be detected early by microtubule destabilization and the repositioning of the centrosome from the cell-cell junction to the cell center. Consistent with their high migration velocities, cells in intermediate states produced low contractile forces compared with epithelial and mesenchymal cells. The high contractile forces in mesenchymal cells powered a retrograde flow pushing the nucleus away from cell adhesion to the extracellular matrix. Therefore, cells in intermediate state had structural and mechanical properties that were distinct but not necessarily intermediate between epithelial and mesenchymal cells. Based on these observations, we found that a panel of triple-negative breast cancer lines had intermediate rather than mesenchymal characteristics suggesting that the structural and mechanical properties of the intermediate state are important for understanding tumor-cell dissemination.

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“…[ 12 ] To standardize those promising cell‐based models, scientists now seek to shape and spatially functionalize (decorate) gels into templates. [ 13–15 ] This has been previously achieved through molding and stamping [ 6,7,16 ] and more recently using light and dedicated chemicals. [ 17–22 ]…”

Section: Figurementioning

confidence: 99%

Tailoring Common Hydrogels into 3D Cell Culture Templates

Pasturel

Strale

Studer

2020

Adv Healthcare Materials

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Physiologically relevant cell‐based models require engineered microenvironments which recapitulate the topographical, biochemical, and mechanical properties encountered in vivo. In this context, hydrogels are the materials of choice. Here a light‐based toolbox is able to craft such microniches out of common place materials. Extensive use of benzophenone photoinitiators and their interaction with oxygen achieves this. First, the oxygen inhibition of radicals is harnessed to photoprint hydrogel topographies. Then the chemical properties of benzophenone are exploited to crosslink and functionalize native hydrogels lacking photosensitive moieties. At last, photoscission is introduced: an oxygen‐driven, benzophenone‐enabled reaction that photoliquefies Matrigel and other common gels. Using these tools, soft hydrogel templates are tailored for cells to grow or self‐organize into standardized structures. The described workflow emerges as an effective microniche manufacturing toolset for 3D cell culture.

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Convergence of microengineering and cellular self-organization towards functional tissue manufacturing

Cited by 105 publications

References 260 publications

Responsive Inverse Opal Scaffolds with Biomimetic Enrichment Capability for Cell Culture

Responsive Inverse Opal Scaffolds with Biomimetic Enrichment Capability for Cell Culture

Biophysical properties of intermediate states of EMT outperform both epithelial and mesenchymal states

Tailoring Common Hydrogels into 3D Cell Culture Templates

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