Ultrathin Polymer Membranes with Patterned, Micrometric Pores for Organs-on-Chips

Costa, Lino; Terekhov, Alexander; Gnecco, Juan; Wikswo, John P.; Hofmeister, William

doi:10.1021/acsami.6b05754

Cited by 26 publications

(31 citation statements)

References 56 publications

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“…Hydrogel‐based 3D matrices can also be used to build pathophysiological tissue barriers in OOC systems, such as BBB, alveolar–capillary barrier, placental barrier, and other functional barriers . For example, a glomerulus‐on‐a‐chip microdevice was developed to reconstitute organ‐level kidney function and model diabetic nephropathy .…”

Section: Hydrogels In Organs‐on‐a‐chip Engineeringmentioning

confidence: 99%

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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The major motivation is to better mimic human physiology and functions at multiscales from the molecular to the cellular, tissue, organ or even whole organism level. Current model systems primarily rely on the monolayer cell cultures and animal models. Simplistic monolayer cultures have their advantages, but they are often significantly different in gene expression, epigenetics, and cell function compared to native 3D tissues. [1,2] Also, they often lack cell-cell and cell-matrix interactions, [2,3] leading to the absence of tissue specific properties. Although animal models are widely used in biomedical research, they fail to faithfully predict human responses in a physiologically relevant manner due to the significant species divergences. [4] The limitations of these systems have provided an impetus for the development of alternative cell-based 3D models in vitro that better resemble the complex functionalities of living organs. Over the last several years, organoids and organ-on-a-chip (OOC), representing the major technological breakthrough, have emerged as two distinct model systems to achieve the same goal of building 3D organotypic models in vitro by bridging the gap between animal models and monolayer cultures. These engineered models are different in terms of cell source, tissue composition, architectural variability, functional features, scales, cellular fidelity, etc. Organoids, primarily evolving from developmental principles, refer to 3D multicellular tissues by self-organization of stem cells or organ-specific progenitors, which can recapitulate the intricate architectures and functionalities of in vivo organs. [5][6][7] Recent breakthroughs in organoid technology have enabled the successful generation of a variety of human organoids, such as the brain, [8,9] intestine, [10,11] liver, [12] kidney, [13,14] lung, [15] etc. These near physiological 3D organoids have garnered momentum for their potential applications in human organ development and disease modeling, drug screening and regenerative medicine. The explosion of organoids research has been catalyzed by the significant progress of stem cell biology and availability of human stem cells. In contrast, the OOC, relying on the bioengineering design principle, is a miniaturized in vitro model that can recreate the functional units of living organs on a microfluidic cell culture device using predifferentiated cells, often cell lines. [1,16] The OOC is primarily evolved from the convergence of tissue engineering and microfabricated technologies, which is characterized by the capability to simulate cellular microenvironment by precise control over fluid flow, mechanical forces and biochemical factors. [4,17] Remarkable progress has been made Significant advances in materials, microscale technology, and stem cell biology have enabled the construction of 3D tissues and organs, which will ultimately lead to more effective diagnostics and therapy. Organoids and organs-on-a-chip (OOC), evolved from developmental biology and bioengineering principles, have e...

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Section: Hydrogels In Organs‐on‐a‐chip Engineeringmentioning

confidence: 99%

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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“…These proteins contain amino acid sequences like arginine-glycine-aspartic acid (RGD), which are potent sites for cell adhesion [54,55]. Cells interact with these sites via integrins, transmembrane proteins [6] erythrocyte oxygenation [7] gut [1,18,19] heart [40] kidney [13] liver [1,3,13,38] lung [1,11,13,42] multi-organ-on-chip (MOC) of liver and heart [47] new membranes for OOCs [52] poly(carbonate) (PC) blood -brain barrier (BBB) [4,43,44] bonding of membrane to chip [51] colon and breast cancer [27] gut [8,9] gut, liver and brain cancer [16] MOC of liver and intestine [29] MOC of liver and skin [29] multiple-layered cultures of fibroblasts, endothelial and mesenchymal cells [41] liver, lung and breast cancer and gut [25] skin [5,23] poly(ethylene terephthalate) (PET) gut [39] heart [28] kidney [15] liver [17,48] microfluidic barrier tissues [2] MOC of liver and cancer [21] white adipose tissue (fat) [26] aliphatic polyesters poly(lactic acid) (PLA) endothelial barrier [33] poly ( liver…”

Section: Need For Mimicking the Extracellular Matrixmentioning

confidence: 99%

Flat and microstructured polymeric membranes in organs-on-chips

Pasman

Grijpma

Stamatialis

et al. 2018

J. R. Soc. Interface.

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In recent years, organs-on-chips (OOCs) have been developed to meet the desire for more realistic cell culture models. These systems introduce microfluidics, mechanical stretch and other physiological stimuli to models, thereby significantly enhancing their descriptive power. In most OOCs, porous polymeric membranes are used as substrates for cell culture. The polymeric material, morphology and shape of these membranes are often suboptimal, despite their importance for achieving ideal cell functionality such as cell-cell interaction and differentiation. The currently used membranes are flat and thus do not account for the shape and surface morphology of a tissue. Moreover, the polymers used for fabrication of these membranes often lack relevant characteristics, such as mechanical properties matching the tissue to be developed and/or cytocompatibility. Recently, innovative techniques have been reported for fabrication of porous membranes with suitable porosity, shape and surface morphology matching the requirements of OOCs. In this paper, we review the state of the art for developing these membranes and discuss their application in OOCs.

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“…1,2 Due to the capabilities of porous membranes in providing biologically relevant cell-cell interactions between the co-cultured cells, these membranes have received significant attention in development of biomimetic platforms to model different tissue and organs including lung, blood brain barrier, kidney, blood vessel, gut, and liver. [3][4][5][6][7][8][9][10][11] While these membranes effectively support cell-cell communication, their role in cellular behaviors including cell migration, extracellular matrix (ECM) development, and cell adhesion is not fully understood and is currently under study.…”

Section: Introductionmentioning

confidence: 99%

Altered Cell-Substrate Behavior on Microporous Membranes is a Result of Disruption and Grip

Allahyari¹,

Gholizadeh²,

Chung³

et al. 2019

Preprint

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Porous membranes are ubiquitous in cell co-culture and tissue-on-a-chip studies. These materials are predominantly chosen for their semi-permeable and size exclusion properties to restrict or permit transmigration and cell-cell communication. However, previous studies have shown pore size, spacing and orientation affect cell behavior including extracellular matrix production and migration. The mechanism behind this behavior is not fully understood. In this study, we fabricated micropatterned non-fouling polyethylene glycol (PEG) islands to mimic pores in order to decouple the effect of surface discontinuity from grip provided by pore wall edges. Similar to porous membranes, we found that the PEG islands hindered fibronectin fibrillogenesis with cells on patterned substrates producing shorter fibrils. Additionally, cell migration speed over micropatterned PEG islands was greater than unpatterned controls, suggesting that disruption of cell-substrate interactions by PEG islands promoted a more dynamic and migratory behavior, similarly to cells migrating on microporous membranes. Preferred cellular directionality during migration was nearly identical between substrates with identically patterned PEG islands and micropores, further confirming disruption of cell-substrate interactions as a common mechanism behind the cellular responses on these substrates. Interestingly, cell spreading and the magnitude of migration speed was significantly greater on porous membranes compared to PEG islands with identical feature size and spacing, suggesting pore edges enhanced cellular grip. These results provide a more complete picture on how porous membranes affect cells which are grown on them in an increasing number of cellular barrier and co-culture studies.

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Ultrathin Polymer Membranes with Patterned, Micrometric Pores for Organs-on-Chips

Cited by 26 publications

References 56 publications

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Flat and microstructured polymeric membranes in organs-on-chips

Altered Cell-Substrate Behavior on Microporous Membranes is a Result of Disruption and Grip

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