Stretchable mesh microelectronics for the biointegration and stimulation of human neural organoids

Li, Thomas L.; Liu, Yuxin; Forró, Csaba; Yang, Xiao; Beker, Levent; Bao, Zhenan; Cui, Bianxiao; Paşca, Sergiu P.

doi:10.1016/j.biomaterials.2022.121825

Cited by 21 publications

(15 citation statements)

References 34 publications

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“…The KiriE platform has several advantages compared to prior technologies 5-14,26 . First, the 3D basket-like geometry of KiriE is designed for stable integration with intact neural organoids in suspension without the need for insertion, slicing or contacting the substrate.…”

Section: Discussionmentioning

confidence: 99%

Kirigami electronics for long-term electrophysiological recording of human neural organoids and assembloids

Yang,

Forró,

et al. 2023

Preprint

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Organoids and assembloids have emerged as a promising platform to model aspects of nervous system development. Long-term, minimally-invasive recordings in these multi-cellular systems are essential for developing disease models. Current technologies, such as patch-clamp, penetrating microelectrodes, planar electrode arrays and substrate-attached flexible electrodes, do not, however, allow chronic recording of organoids in suspension, which is necessary to preserve their architecture. Inspired by the art of kirigami, we developed flexible electronics that transition from a 2D pattern to a 3D basket-like configuration to accommodate the long-term culture of organoids in suspension. This platform, named kirigami electronics (KiriE), integrates with and enables chronic recording of cortical organoids while preserving morphology, cytoarchitecture, and cell composition. KiriE can be integrated with optogenetic and pharmacological stimulation and model disease. Moreover, KiriE can capture activity in cortico-striatal assembloids. Moving forward, KiriE could reveal disease phenotypes and activity patterns underlying the assembly of the nervous system.

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Section: Discussionmentioning

confidence: 99%

Kirigami electronics for long-term electrophysiological recording of human neural organoids and assembloids

Yang,

Forró,

et al. 2023

Preprint

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“…Combined with exogenous electrical stimulation, studies have reported that exogenous electrical stimulation could transmit electric signals/impulses and induce changes in endogenous electrical activities of neural organoids. [109] For example, Li et al developed a novel stretchable soft mesh electrode system for the stimulation of human neural organoids [109] (Figure 5G). The study showed that the mesh was biocompatible and integrated with human cortical organoids; and demonstrated that electrical stimulation through the meshes could evoke calcium signals and regulate the electrical performance of organoids at varying current amplitude, pulse number, and pulse strain frequency.…”

Section: Electrophysiological Microsystemmentioning

confidence: 99%

“…Reproduced with permission. [ 109 ] Copyright 2022, Elsevier. H) Photoreceptor‐binding upconversion nanoparticles (pbUCNPs) anchored to photoreceptors could serve as ocular injectable naturally invisible near‐infrared light (NIR) transducers and extend the visual spectrum.…”

Section: Building Physical Microenvironment For Neural Organoidsmentioning

confidence: 99%

Section: Building Physical Microenvironment For Neural Organoidsmentioning

confidence: 99%

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Engineering the Physical Microenvironment into Neural Organoids for Neurogenesis and Neurodevelopment

Li,

Sun,

Hou

et al. 2023

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Understanding the signals from the physical microenvironment is critical for deciphering the processes of neurogenesis and neurodevelopment. The discovery of how surrounding physical signals shape human developing neurons is hindered by the bottleneck of conventional cell culture and animal models. Notwithstanding neural organoids provide a promising platform for recapitulating human neurogenesis and neurodevelopment, building neuronal physical microenvironment that accurately mimics the native neurophysical features is largely ignored in current organoid technologies. Here, it is discussed how the physical microenvironment modulates critical events during the periods of neurogenesis and neurodevelopment, such as neural stem cell fates, neural tube closure, neuronal migration, axonal guidance, optic cup formation, and cortical folding. Although animal models are widely used to investigate the impacts of physical factors on neurodevelopment and neuropathy, the important roles of human stem cell‐derived neural organoids in this field are particularly highlighted. Considering the great promise of human organoids, building neural organoid microenvironments with mechanical forces, electrophysiological microsystems, and light manipulation will help to fully understand the physical cues in neurodevelopmental processes. Neural organoids combined with cutting‐edge techniques, such as advanced atomic force microscopes, microrobots, and structural color biomaterials might promote the development of neural organoid‐based research and neuroscience.

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“…Bioelectricity of cells and tissues is essential to assess health at the microscale in a variety of scenarios, from single-cell electrophysiological recording to cellular proliferation. It is well assessed that action potentials, i.e., rapid polarization and depolarization of the cellular membrane observed in neuronal and muscle cells, reflect their physiological state and have been extensively targeted as a biomarker to design in vitro drug testing platforms. − However, the majority of cells in the human body do not fire action potentials, their electrical activity is expressed in the form of static potentials given by the passage of ions in and out of the membrane at equilibrium, and they communicate in a narrower signal range. It follows that much less is known with regards to the electrical activity of non-excitable cells and tissues, and this can be primarily attributed to the lack of methods for reliably monitoring these parameters .…”

mentioning

confidence: 99%

Passive Recording of Bioelectrical Signals from Non-Excitable Cells by Fluorescent Mirroring

et al. 2023

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Bioelectrical variations trigger different cell responses, including migration, mitosis, and mutation. At the tissue level, these actions result in phenomena such as wound healing, proliferation, and pathogenesis. Monitoring these mechanisms dynamically is highly desirable in diagnostics and drug testing. However, existing technologies are invasive: either they require physical access to the intracellular compartments, or they imply direct contact with the cellular medium. Here, we present a novel approach for the passive recording of electrical signals from non-excitable cells adhering to 3D microelectrodes, based on optical mirroring. Preliminary results yielded a fluorescence intensity output increase of the 5,8% in the presence of a HEK-293 cell on the electrode compared to bare microelectrodes. At present, this technology may be employed to evaluate cell−substrate adhesion and monitor cell proliferation. Further refinements could allow extrapolating quantitative data on surface charges and resting potential to investigate the electrical phenomena involved in cell migration and cancer progression.

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Stretchable mesh microelectronics for the biointegration and stimulation of human neural organoids

Cited by 21 publications

References 34 publications

Kirigami electronics for long-term electrophysiological recording of human neural organoids and assembloids

Kirigami electronics for long-term electrophysiological recording of human neural organoids and assembloids

Engineering the Physical Microenvironment into Neural Organoids for Neurogenesis and Neurodevelopment

Passive Recording of Bioelectrical Signals from Non-Excitable Cells by Fluorescent Mirroring

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