Endothelial vacuolization induced by highly permeable silicon membranes

Nehilla, Barrett J.; Nataraj, Nakul; Gaborski, Thomas R.; McGrath, James L.

doi:10.1016/j.actbio.2014.07.022

Cited by 11 publications

(16 citation statements)

References 41 publications

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“…The RTP treatment significantly delays the biodegradation rate of pnc-Si (Agrawal et al, 2010). Pnc-Si samples were secured in custom polypropylene housings (Harbec Plastics, Inc., Ontario, NY) with a biocompatible O-ring to form pnc-Si transwells (Nehilla et al, 2014). The pnc-Si transwells were autoclaved before use.…”

Section: Methodsmentioning

confidence: 99%

“…Our laboratories have pioneered the development of ultrathin silicon-based membranes for a variety of applications including cell culture (Striemer et al, 2007; Nehilla et al, 2014; Agrawal et al, 2010; DesOrmeaux et al, 2014; Mazzocchi et al, 2014; Carter et al, 2017; Casillo et al, 2017). The thickness of these ‘nanomembranes’ is between 15 nm and 400 nm with porosities as high as 30%.…”

Section: Introductionmentioning

confidence: 99%

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Finite element modeling to analyze TEER values across silicon nanomembranes

Khire

Nehilla

Getpreecharsawas

et al. 2018

Biomed Microdevices

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Silicon nanomembranes are ultrathin, highly permeable, optically transparent and biocompatible substrates for the construction of barrier tissue models. Trans-epithelial/endothelial electrical resistance (TEER) is often used as a non-invasive, sensitive and quantitative technique to assess barrier function. The current study characterizes the electrical behavior of devices featuring silicon nanomembranes to facilitate their application in TEER studies. In conventional practice with commercial systems, raw resistance values are multiplied by the area of the membrane supporting cell growth to normalize TEER measurements. We demonstrate that under most circumstances, this multiplication does not 'normalize' TEER values as is assumed, and that the assumption is worse if applied to nanomembrane chips with a limited active area. To compare the TEER values from nanomembrane devices to those obtained from conventional polymer track-etched (TE) membranes, we develop finite element models (FEM) of the electrical behavior of the two membrane systems. Using FEM and parallel cell-culture experiments on both types of membranes, we successfully model the evolution of resistance values during the growth of endothelial monolayers. Further, by exploring the relationship between the models we develop a 'correction' function, which when applied to nanomembrane TEER, maps to experiments on conventional TE membranes. In summary, our work advances the the utility of silicon nanomembranes as substrates for barrier tissue models by developing an interpretation of TEER values compatible with conventional systems.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Finite element modeling to analyze TEER values across silicon nanomembranes

Khire

Nehilla

Getpreecharsawas

et al. 2018

Biomed Microdevices

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“…Previously, our lab has developed a variety of ultrathin (50–100 nm), highly permeable nanoporous membranes for use in cell culture, and biological separations . These membranes contain pores ranging in size from 15 to 100 nm with pore to pore spacing less than 100 nm.…”

Section: Introductionmentioning

confidence: 99%

Ultrathin Dual‐Scale Nano‐ and Microporous Membranes for Vascular Transmigration Models

Salminen

Zhang

Madejski

et al. 2019

Small

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Selective cellular transmigration across the microvascular endothelium regulates innate and adaptive immune responses, stem cell localization, and cancer cell metastasis. Integration of traditional microporous membranes into microfluidic vascular models permits the rapid assay of transmigration events but suffers from poor reproduction of the cell permeable basement membrane. Current microporous membranes in these systems have large nonporous regions between micropores that inhibit cell communication and nutrient exchange on the basolateral surface reducing their physiological relevance. Here, the use of 100 nm thick continuously nanoporous silicon nitride membranes as a base substrate for lithographic fabrication of 3 µm pores is presented, resulting in a highly porous (≈30%), dual‐scale nano‐ and microporous membrane for use in an improved vascular transmigration model. Ultrathin membranes are patterned using a precision laser writer for cost‐effective, rapid micropore design iterations. The optically transparent dual‐scale membranes enable complete observation of leukocyte egress across a variety of pore densities. A maximal density of ≈14 micropores per cell is discovered beyond which cell–substrate interactions are compromised giving rise to endothelial cell losses under flow. Addition of a subluminal extracellular matrix rescues cell adhesion, allowing for the creation of shear‐primed endothelial barrier models on nearly 30% continuously porous substrates.

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“…[6] Literature indicates that porous membranes are an essential component for compartmentalized cell co-cultures and to support a tissue barrier. [6][7][8][9][10][11][12][13][14][15] However, most barrier models incorporate commercially available track-etched membranes such as those found in transwell, fiber-based, or micro-fluidic systems with a high thickness compared to the basal laminae in vivo (>10 µm vs. ~300 nm). By using available materials, the porosity cannot be adequately engineered, leading to low porosity, random pore distribution, and limited size control, potentially biasing physiological multi-cellular interplay, especially during co-culture conditions.…”

Section: Introductionmentioning

confidence: 99%

Robust and Gradient Thickness Porous Membranes forIn VitroModeling of Physiological Barriers

Gholizadeh

Allahyari

Robert

et al. 2020

Preprint

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Porous membranes are fundamental elements for tissue-chip barrier and co-culture models. However, the exaggerated thickness of commonly available membranes impedes an accurate in vitro reproduction of the biological multi-cellular continuum as it occurs in vivo. Existing techniques to fabricate membranes such as solvent cast, spin-coating, sputtering and PE-CVD result in uniform thickness films. To understand critical separation distances for various barrier and co-culture models, a gradient thickness membrane is needed. Here, we developed a robust method to generate ultrathin porous parylene C (UPP) membranes not just with precise thicknesses down to 300 nm, but with variable gradients in thicknesses, while at the same time having porosities up to 25%. We also show surface etching and increased roughness lead to improved cell attachment. Next, we examined the mechanical properties of UPP membranes with varying porosity and thickness and fit our data to previously published models, which can help determine practical upper limits of porosity and lower limits of thickness. Lastly, we validate a straightforward approach allowing the successful integration of the UPP membranes into a prototyped 3D-printed scaffold enabling in vitro barrier modeling and investigation of cell-cell interplay over variable distances using thickness gradients.

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Endothelial vacuolization induced by highly permeable silicon membranes

Cited by 11 publications

References 41 publications

Finite element modeling to analyze TEER values across silicon nanomembranes

Finite element modeling to analyze TEER values across silicon nanomembranes

Ultrathin Dual‐Scale Nano‐ and Microporous Membranes for Vascular Transmigration Models

Robust and Gradient Thickness Porous Membranes forIn VitroModeling of Physiological Barriers

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