Oxygen control: the often overlooked but essential piece to create better<i>in vitro</i>systems

Palacio-Castañeda, Valentina; Velthuijs, Niels; Gac, Séverine Le; Verdurmen, Wouter P. R.

doi:10.1039/d1lc00603g

Cited by 27 publications

(28 citation statements)

References 175 publications

(330 reference statements)

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“…Additionally, as muscle tissue matures and increases in volume it will change the material properties of the substrate, altering the rate at which oxygen can diffuse through the device. Experimental measurement of oxygen gradients is difficult [ 8 ], and construction and trialling of prototype devices is costly both in terms of materials required and the time taken to engineer and run. Through numerical modelling, in silico experiments can be used to estimate transport of oxygen within the device via advection through media flow, diffusion and cell consumption in a fast and inexpensive manner [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Mathematical modelling of oxygen transport in a muscle-on-chip device

et al. 2022

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Muscle-on-chip devices aim to recapitulate the physiological characteristics of in vivo muscle tissue and so maintaining levels of oxygen transported to cells is essential for cell survival and for providing the normoxic conditions experienced in vivo . We use finite-element method numerical modelling to describe oxygen transport and reaction in a proposed three-dimensional muscle-on-chip bioreactor with embedded channels for muscle cells and growth medium. We determine the feasibility of ensuring adequate oxygen for muscle cell survival in a device sealed from external oxygen sources and perfused via medium channels. We investigate the effects of varying elements of the bioreactor design on oxygen transport to optimize muscle tissue yield and maintain normoxic conditions. Successful co-culturing of muscle cells with motor neurons can boost muscle tissue function and so we estimate the maximum density of seeded neurons supported by oxygen concentrations within the bioreactor. We show that an enclosed bioreactor can provide sufficient oxygen for muscle cell survival and growth. We define a more efficient arrangement of muscle and perfusion chambers that can sustain a predicted 50% increase in maximum muscle volume per perfusion vessel. A study of simulated bioreactors provides functions for predicting bioreactor designs with normoxic conditions for any size of perfusion vessel, muscle chamber and distance between chambers.

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Section: Introductionmentioning

confidence: 99%

Mathematical modelling of oxygen transport in a muscle-on-chip device

et al. 2022

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“…13 To improve and accurately control oxygen supply and diffusion in a microfluidic device, two main approaches are used: engineering and chemical approaches. 164 In engineering approach, the oxygen diffusion is controlled by combining oxygen-permeable (PDMS) and -impermeable (e.g., glass, PMMA, PS and PC) materials to build the microfluidic device. [164][165][166] The chemical approach involves adding oxygen or oxygen scavenging/generating chemicals to the perfused fluid.…”

Section: Contribution Of Ooc Technology To the Improvement Of In Vitr...mentioning

confidence: 99%

“…164 In engineering approach, the oxygen diffusion is controlled by combining oxygen-permeable (PDMS) and -impermeable (e.g., glass, PMMA, PS and PC) materials to build the microfluidic device. [164][165][166] The chemical approach involves adding oxygen or oxygen scavenging/generating chemicals to the perfused fluid. 164,167 OoC technology allows also the control of chemicals and hormones gradients to generate metabolic zonation.…”

Section: Contribution Of Ooc Technology To the Improvement Of In Vitr...mentioning

confidence: 99%

“…[164][165][166] The chemical approach involves adding oxygen or oxygen scavenging/generating chemicals to the perfused fluid. 164,167 OoC technology allows also the control of chemicals and hormones gradients to generate metabolic zonation. 13,168 Other advantages of the dynamic flow in OoC include the ability to provide controlled shear stress emulating the in vivo mechanical stimulus applied by blood flow on cells and the regulation of drugs/metabolites concentrations, which facilitated drug screening.…”

Section: Contribution Of Ooc Technology To the Improvement Of In Vitr...mentioning

confidence: 99%

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Liver organ-on-chip models for toxicity studies and risk assessment

et al. 2022

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“…If oxygen gradient is established in a single culture chamber, the exact location of the cells within the chamber corresponds to the oxygen environment defining the cell response. Most often, the analyses are image-based because once cells are detached from the culture compartment for sample analysis, the information about the spatial location and the corresponding oxygen environment of the cells is lost (Palacio-Castañeda et al 2022 ). Rexius-Hall et al resolved this by constructing two sets of oxygen supply channels beneath the cell culture compartment, inducing a hypoxic environment on the one side and a normoxia environment on the other.…”

Section: Introductionmentioning

confidence: 99%

Compartmentalized organ-on-a-chip structure for spatiotemporal control of oxygen microenvironments

Tornberg

Välimäki

Valaskivi

et al. 2022

Biomed Microdevices

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Hypoxia is a condition where tissue oxygen levels fall below normal levels. In locally induced hypoxia due to blood vessel blockage, oxygen delivery becomes compromised. The site where blood flow is diminished the most forms a zero-oxygen core, and different oxygenation zones form around this core with varying oxygen concentrations. Naturally, these differing oxygen microenvironments drive cells to respond according to their oxygenation status. To study these cellular processes in laboratory settings, the cellular gas microenvironments should be controlled rapidly and precisely. In this study, we propose an organ-on-a-chip device that provides control over the oxygen environments in three separate compartments as well as the possibility of rapidly changing the corresponding oxygen concentrations. The proposed device includes a microfluidic channel structure with three separate arrays of narrow microchannels that guide gas mixtures with desired oxygen concentrations to diffuse through a thin gas-permeable membrane into cell culture areas. The proposed microfluidic channel structure is characterized using a 2D ratiometric oxygen imaging system, and the measurements confirm that the oxygen concentrations at the cell culture surface can be modulated in a few minutes. The structure is capable of creating hypoxic oxygen tension, and distinct oxygen environments can be generated simultaneously in the three compartments. By combining the microfluidic channel structure with an open-well coculture device, multicellular cultures can be established together with compartmentalized oxygen environment modulation. We demonstrate that the proposed compartmentalized organ-on-a-chip structure is suitable for cell culture.

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Oxygen control: the often overlooked but essential piece to create betterin vitrosystems

Abstract: Variations in oxygen levels play key roles in numerous physiological and pathological processes, but are often not properly controlled in in vitro models, introducing a significant bias in experimental outcomes....

Cited by 27 publications

References 175 publications

Mathematical modelling of oxygen transport in a muscle-on-chip device

Mathematical modelling of oxygen transport in a muscle-on-chip device

Liver organ-on-chip models for toxicity studies and risk assessment

Compartmentalized organ-on-a-chip structure for spatiotemporal control of oxygen microenvironments

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