Human neuromuscular junction on micro-structured microfluidic devices implemented with a custom micro electrode array (MEA)

Duc, Pauline; Vignes, Michel; Hugon, Gérald; Sebban, Audrey; Carnac, Gilles; Malyshev, Eugene; Charlot, B.; Rage, Florence

doi:10.1039/d1lc00497b

Cited by 26 publications

(22 citation statements)

References 58 publications

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“…Such a multi‐functional platform is promising for the development of technologies to characterize neural circuits and neuromuscular units with higher sensitivity as compared to the traditional approaches, such as intracellular calcium imaging. [ 335 ]…”

Section: Microfluidics For Bio‐actuatorsmentioning

confidence: 99%

“…Duc et al exploited soft lithography and custom MEAs to engineer a microfluidic model of human neuromuscular junction on a specific pattern of electrodes to stimulate presynaptic axons and record postsynaptic muscle activity (Figure 6F). [335] In this platform the group demonstrated that not only the achievement of a mature and functional neuromuscular modeling via microstructuring of the chip and the cell growth substrates, but also that the electrical activation of motor neurons triggered recordable extracellular muscle action potentials. Such a multi-functional platform is promising for the development of technologies to characterize neural circuits and neuromuscular units with higher sensitivity as compared to the traditional approaches, such as intracellular calcium imaging.…”

Section: Microfluidics In Muscle Tissue Engineeringmentioning

confidence: 99%

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Microfluidic Tissue Engineering and Bio‐Actuation

et al. 2022

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Bio‐hybrid technologies aim to replicate the unique capabilities of biological systems that could surpass advanced artificial technologies. Soft bio‐hybrid robots consist of synthetic and living materials and have the potential to self‐assemble, regenerate, work autonomously, and interact safely with other species and the environment. Cells require a sufficient exchange of nutrients and gases, which is guaranteed by convection and diffusive transport through liquid media. The functional development and long‐term survival of biological tissues in vitro can be improved by dynamic flow culture, but only microfluidic flow control can develop tissue with fine structuring and regulation at the microscale. Full control of tissue growth at the microscale will eventually lead to functional macroscale constructs, which are needed as the biological component of soft bio‐hybrid technologies. This review summarizes recent progress in microfluidic techniques to engineer biological tissues, focusing on the use of muscle cells for robotic bio‐actuation. Moreover, the instances in which bio‐actuation technologies greatly benefit from fusion with microfluidics are highlighted, which include: the microfabrication of matrices, biomimicry of cell microenvironments, tissue maturation, perfusion, and vascularization.

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Section: Microfluidics For Bio‐actuatorsmentioning

confidence: 99%

Section: Microfluidics In Muscle Tissue Engineeringmentioning

confidence: 99%

Microfluidic Tissue Engineering and Bio‐Actuation

et al. 2022

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“…In 2005, Taylor and colleagues reported a microfluidic multi-compartment chamber that can be easily replicated by soft-lithography ( Taylor et al, 2005 ) and installed on cell culture dishes (e.g., culture dish, glass coverslip, and recording chips). Since then, there have been various cell culture assays including axon growth ( Park et al, 2014 ; Taylor et al, 2015 ), synapse manipulation ( Taylor et al, 2010 ), synapse remodeling ( Nagendran et al, 2017 ), axonal transport ( Moutaux et al, 2018b ), stem cell-derived neuron migration ( Lee et al, 2014 ), and neuron/non-neuronal cell (e.g., glia, cardiomyocyte, and muscle fiber) interaction ( Duc et al, 2021 ; Hosmane et al, 2010 ; Park et al, 2012 ; Takeuchi et al, 2011 ). More applications can be found elsewhere ( Neto et al, 2016 ).…”

Section: Cell Patterning Techniquesmentioning

confidence: 99%

“…On the MEA, the DG-CA3-CA1 ( Brewer et al, 2013 ) and cortical-thalamic network ( Kanagasabapathi et al, 2012 ) were developed, and their spike propagation and burst behavior were examined. Furthermore, different cell types, such as cardiomyocytes with neurons in the peripheral nervous system ( Takeuchi et al, 2011 ), myoblasts with motor neurons ( Duc et al, 2021 ), or stem cell-derived neurons with primary neurons in the central nervous system ( Takayama et al, 2012 ) were also co-cultured to interrogate their interactions via electrophysiological observation.…”

Section: Microelectrode Array For Analyzing the Functional Connectivi...mentioning

confidence: 99%

Neurons-on-a-Chip: In Vitro NeuroTools

Hong

Nam

2022

Molecules and Cells

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Neurons-on-a-Chip technology has been developed to provide diverse in vitro neuro-tools to study neuritogenesis, synaptogensis, axon guidance, and network dynamics. The two core enabling technologies are soft-lithography and microelectrode array technology. Soft lithography technology made it possible to fabricate microstamps and microfluidic channel devices with a simple replica molding method in a biological laboratory and innovatively reduced the turn-around time from assay design to chip fabrication, facilitating various experimental designs. To control nerve cell behaviors at the single cell level via chemical cues, surface biofunctionalization methods and micropatterning techniques were developed. Microelectrode chip technology, which provides a functional readout by measuring the electrophysiological signals from individual neurons, has become a popular platform to investigate neural information processing in networks. Due to these key advances, it is possible to study the relationship between the network structure and functions, and they have opened a new era of neurobiology and will become standard tools in the near future.

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“…The first generation of these body-on-a-chip-models already exists [ 241 ], and the incorporation of MEAs into the models can provide important information on the electrical activity of not only the brain-part but also other tissues such as the heart [ 242 ], retina [ 243 ] and pancreatic beta cells [ 244 ]. Furthermore, connecting peripheral neurons to CNS neurons in a body-on-a-chip is an interesting option [ 245 ], and the function of the human neuromuscular junction was recently modeled in a microfluidic device on MEA [ 246 ].…”

Section: Future Directionsmentioning

confidence: 99%

Functional Characterization of Human Pluripotent Stem Cell-Derived Models of the Brain with Microelectrode Arrays

Pelkonen

Pistono

Klecki

et al. 2021

Cells

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Human pluripotent stem cell (hPSC)-derived neuron cultures have emerged as models of electrical activity in the human brain. Microelectrode arrays (MEAs) measure changes in the extracellular electric potential of cell cultures or tissues and enable the recording of neuronal network activity. MEAs have been applied to both human subjects and hPSC-derived brain models. Here, we review the literature on the functional characterization of hPSC-derived two- and three-dimensional brain models with MEAs and examine their network function in physiological and pathological contexts. We also summarize MEA results from the human brain and compare them to the literature on MEA recordings of hPSC-derived brain models. MEA recordings have shown network activity in two-dimensional hPSC-derived brain models that is comparable to the human brain and revealed pathology-associated changes in disease models. Three-dimensional hPSC-derived models such as brain organoids possess a more relevant microenvironment, tissue architecture and potential for modeling the network activity with more complexity than two-dimensional models. hPSC-derived brain models recapitulate many aspects of network function in the human brain and provide valid disease models, but certain advancements in differentiation methods, bioengineering and available MEA technology are needed for these approaches to reach their full potential.

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Human neuromuscular junction on micro-structured microfluidic devices implemented with a custom micro electrode array (MEA)

Abstract: Microfluidic devices were coupled with custom MEA and used for co-culture of human motor neurons and muscles. This allowed to assess human NMJ activity by electrical stimulation of axons and recording of subsequent muscle action potentials.

Cited by 26 publications

References 58 publications

Microfluidic Tissue Engineering and Bio‐Actuation

Microfluidic Tissue Engineering and Bio‐Actuation

Neurons-on-a-Chip: In Vitro NeuroTools

Functional Characterization of Human Pluripotent Stem Cell-Derived Models of the Brain with Microelectrode Arrays

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