Generating linear oxygen gradients across 3D cell cultures with block-layered oxygen controlled chips (BLOCCs)

Boyce, Matthew W.; Simke, William C.; Kenney, Rachael M.; Lockett, Matthew R.

doi:10.1039/c9ay01690b

Cited by 14 publications

(13 citation statements)

References 37 publications

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“…Although there have been major efforts in developing methods to control and measure the oxygen tension in microfluidic devices, as discussed in the previous sections, usually these devices have only been validated by confirming well-known biological or pathological processes affected by oxygen levels, as an understandable first proof-of-concept step. Nevertheless, several studies have already provided interesting insights, e.g., with respect to the relation between oxygen levels and cell migration, 82,87,[93][94][95][96][97][114][115][116] ROS production, 74,[117][118][119] activity of HIFs 88,120,121 and metabolic changes. 77,79,122,123 Other work has focused on intermittent vs. chronic hypoxia 81,83,87,124 or investigated targeting of hypoxia by hypoxia-responsive drugs.…”

Section: Biological Applications Of Hypoxia In Microfluidic Devicesmentioning

confidence: 99%

“…Specifically, the device was stratified in four areas based on the oxygen tension, and in areas of the device where the oxygen tension was below 27 mmHg O 2 (∼3.5% O 2 ) a higher oxidative stress was found that was associated with a greater hypoxic response, which was not the case in devices not exposed to an oxygen gradient, where the eGFP intensity did not change significantly. 120 Rexius-Hall et al investigated the cellular response of human lung microvascular endothelial cells to oxygen tension in real-time using an open-well configuration equipped with two meandering gas channels below (device depicted in Fig. 3E top).…”

Section: Activity Of Hifs and Hypoxia-triggered Metabolic Changesmentioning

confidence: 99%

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

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Section: Biological Applications Of Hypoxia In Microfluidic Devicesmentioning

confidence: 99%

Section: Activity Of Hifs and Hypoxia-triggered Metabolic Changesmentioning

confidence: 99%

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

et al. 2022

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“…In particular, this chip was designed to have cell-containing chambers in the center between two lateral parallel channels, where oxygenated and deoxygenated gas mixtures were flowed to impose physio-pathologically-relevant O 2 gradients in the cell-seeded regions. O 2 gradients and resulting cellular responses were simultaneously mapped in real-time to examine whether these cells modify their activity proportionally to O 2 tensions [162].…”

Section: Optical Biosensorsmentioning

confidence: 99%

Biosensors to Monitor Cell Activity in 3D Hydrogel-Based Tissue Models

Fedi

Vitale

Giannoni

et al. 2022

Sensors

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Three-dimensional (3D) culture models have gained relevant interest in tissue engineering and drug discovery owing to their suitability to reproduce in vitro some key aspects of human tissues and to provide predictive information for in vivo tests. In this context, the use of hydrogels as artificial extracellular matrices is of paramount relevance, since they allow closer recapitulation of (patho)physiological features of human tissues. However, most of the analyses aimed at characterizing these models are based on time-consuming and endpoint assays, which can provide only static and limited data on cellular behavior. On the other hand, biosensing systems could be adopted to measure on-line cellular activity, as currently performed in bi-dimensional, i.e., monolayer, cell culture systems; however, their translation and integration within 3D hydrogel-based systems is not straight forward, due to the geometry and materials properties of these advanced cell culturing approaches. Therefore, researchers have adopted different strategies, through the development of biochemical, electrochemical and optical sensors, but challenges still remain in employing these devices. In this review, after examining recent advances in adapting existing biosensors from traditional cell monolayers to polymeric 3D cells cultures, we will focus on novel designs and outcomes of a range of biosensors specifically developed to provide real-time analysis of hydrogel-based cultures.

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“…Fibroblast migration increased when myocytes were exposed to higher levels of ischemia (generated through taller stacks) and was reduced in the absence of cardiac myocytes or with the pharmacological inhibition of TGF-β ( 27 ). Other methods have been developed that similarly modify hydrogels to generate oxygen gradients ( 67 ) by using oxygen-consuming enzymes during hydrogel cross-linking ( 68 , 69 ), embedding a hydrogel between gas flow channels ( 70 ), or linearly increasing cell density and thus oxygen consumption rates ( 71 ), but these methods have not yet been implemented to model post-infarct myocardium.…”

Section: In Vitro Models Of Myocardial Ischemia and Hypoxiamentioning

confidence: 99%

Engineering the Cellular Microenvironment of Post-infarct Myocardium on a Chip

Khalil

McCain

2021

Front. Cardiovasc. Med.

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Myocardial infarctions are one of the most common forms of cardiac injury and death worldwide. Infarctions cause immediate necrosis in a localized region of the myocardium, which is followed by a repair process with inflammatory, proliferative, and maturation phases. This repair process culminates in the formation of scar tissue, which often leads to heart failure in the months or years after the initial injury. In each reparative phase, the infarct microenvironment is characterized by distinct biochemical, physical, and mechanical features, such as inflammatory cytokine production, localized hypoxia, and tissue stiffening, which likely each contribute to physiological and pathological tissue remodeling by mechanisms that are incompletely understood. Traditionally, simplified two-dimensional cell culture systems or animal models have been implemented to elucidate basic pathophysiological mechanisms or predict drug responses following myocardial infarction. However, these conventional approaches offer limited spatiotemporal control over relevant features of the post-infarct cellular microenvironment. To address these gaps, Organ on a Chip models of post-infarct myocardium have recently emerged as new paradigms for dissecting the highly complex, heterogeneous, and dynamic post-infarct microenvironment. In this review, we describe recent Organ on a Chip models of post-infarct myocardium, including their limitations and future opportunities in disease modeling and drug screening.

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Generating linear oxygen gradients across 3D cell cultures with block-layered oxygen controlled chips (BLOCCs)

Abstract: BLOCCs are readily assembled structures of laser cut acrylic and silicone, capable of imposing physiologically relevant oxygen gradients across 3D cell cultures. With sensors and cell-based readouts, we quantified cell-microenvironment relationships.

Cited by 14 publications

References 37 publications

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

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

Biosensors to Monitor Cell Activity in 3D Hydrogel-Based Tissue Models

Engineering the Cellular Microenvironment of Post-infarct Myocardium on a Chip

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