Integrated biocircuits: engineering functional multicellular circuits and devices

Prox, Jordan D.; Smith, Tory; Holl, Chad; Chehade, Nick; Guo, Liang

doi:10.1088/1741-2552/aaa906

Cited by 9 publications

(10 citation statements)

References 72 publications

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“…Most neural interfaces employ an electrical interface to the tissue, where small stimulating or recording electrodes are placed in proximity to the tissues of interest . Electrical stimulating devices impose an electrical field which modulates the behavior of cells in that region, while recording interfaces measure either the activity of single or multiple cells in a region or the localized electrical field potentials.…”

Section: Introductionmentioning

confidence: 93%

Biological Considerations of Optical Interfaces for Neuromodulation

Hart

Kameneva

Wise

et al. 2019

Advanced Optical Materials

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Section: Introductionmentioning

confidence: 93%

Biological Considerations of Optical Interfaces for Neuromodulation

Hart

Kameneva

Wise

et al. 2019

Advanced Optical Materials

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“…1d). The fundamental limitation of bioelectronic medicine caused by the loss of neural fibers or target cell populations can be overcome through advanced regenerative medicine combined with functional living tissue implants [53, 96] to form integrated biocircuits [85] and may provide life-long solutions for chronic diseases such as T1D.…”

Section: Bioelectronic Medicine – Targeting the Nervous System To Conmentioning

confidence: 99%

“…Biocircuit-controlled, smart functional living tissue implants made of autologous materials hold the promise to overcome the primary challenge of chronically implanted electronic devices, namely they are free from foreign body responses and rejection [85]. Such smart biocircuit implants constructed using patient-derived induced pluripotent stem cells (iPSCs) contain self-presenting immune molecules and therefore will seamlessly integrate into the host and provide physiological stimulation, thereby surmounting the difficulties in present biotic-abiotic interfaces.…”

Section: Future Direction: Transplantable Smart Biocircuit Implantsmentioning

confidence: 99%

“…Transplanted, stem cell-derived β-cell clusters lack this neural input. In this review, we will show the progress from pharmaceutical to bioelectronics to manage metabolic functions and further suggest a future direction towards biological neuromodulation using rationally-designed, multicellular biological circuits ( biocircuits for short) of an autologous origin [85]. We will explore emerging biological engineering strategies to produce functional living tissue implants [53, 96] to restore or replace functional circuits lost due to injury or disease.…”

Section: Introductionmentioning

confidence: 99%

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Neuromodulation of metabolic functions: from pharmaceuticals to bioelectronics to biocircuits

et al. 2019

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Neuromodulation of central and peripheral neural circuitry brings together neurobiologists and neural engineers to develop advanced neural interfaces to decode and recapitulate the information encoded in the nervous system. Dysfunctional neuronal networks contribute not only to the pathophysiology of neurological diseases, but also to numerous metabolic disorders. Many regions of the central nervous system (CNS), especially within the hypothalamus, regulate metabolism. Recent evidence has linked obesity and diabetes to hyperactive or dysregulated autonomic nervous system (ANS) activity. Neural regulation of metabolic functions provides access to control pathology through neuromodulation. Metabolism is defined as cellular events that involve catabolic and/or anabolic processes, including control of systemic metabolic functions, as well as cellular signaling pathways, such as cytokine release by immune cells. Therefore, neuromodulation to control metabolic functions can be used to target metabolic diseases, such as diabetes and chronic inflammatory diseases. Better understanding of neurometabolic circuitry will allow for targeted stimulation to modulate metabolic functions. Within the broad category of metabolic functions, cellular signaling, including the production and release of cytokines and other immunological processes, is regulated by both the CNS and ANS. Neural innervations of metabolic (e.g. pancreas) and immunologic (e.g. spleen) organs have been understood for over a century, however, it is only now becoming possible to decode the neuronal information to enable exogenous controls of these systems. Future interventions taking advantage of this progress will enable scientists, engineering and medical doctors to more effectively treat metabolic diseases.

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“…Engineering neuronal network topology requires a combination of methods for controlled cell placement and growth. Several techniques for controlling these parameters in vitro have been proposed in the literature (reviewed in refs and ). The most widely used methods create patterns of cell-adhesive and/or cell-repellent promoting zones on 2D substrates (chemical patterning, e.g., microcontact printing) ,− or create 3D structures that physically confine and guide neurons (physical patterning, e.g., microfluidics). ,− Typically, both approaches take advantage of conventional soft lithography for stamping/structuring the desired patterns at the microscale (e.g., microspots/microwells) by using biocompatible silicones, most often poly(dimethylsiloxane) (PDMS), which are replicated from a photolithographically patterned master mold.…”

mentioning

confidence: 99%

Nanoscale Patterning of In Vitro Neuronal Circuits

Mateus

Weaver

Swaay³

et al. 2022

ACS Nano

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Methods for patterning neurons in vitro have gradually improved and are used to investigate questions that are difficult to address in or ex vivo. Though these techniques guide axons between groups of neurons, multiscale control of neuronal connectivity, from circuits to synapses, is yet to be achieved in vitro. As studying neuronal circuits with synaptic resolution in vivo poses significant challenges, we present an in vitro alternative to validate biophysical and computational models. In this work we use a combination of electron beam lithography and photolithography to create polydimethylsiloxane (PDMS) structures with features ranging from 150 nm to a few millimeters. Leveraging the difference between average axon and dendritic spine diameters, we restrict axon growth while allowing spines to pass through nanochannels to guide synapse formation between small groups of neurons (i.e., nodes). We show this technique can be used to generate large numbers of isolated feed-forward circuits where connections between nodes are restricted to regions connected by nanochannels. Using a genetically encoded calcium indicator in combination with fluorescently tagged postsynaptic protein, PSD-95, we demonstrate functional synapses can form in this region.

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Integrated biocircuits: engineering functional multicellular circuits and devices

Abstract: We provide our perspective and propose new insights into the future of neuromodulaion devices within the scope of living cellular systems that can be applied in designing more reliable and biocompatible stimulation-based neuroprosthetics.

Cited by 9 publications

References 72 publications

Biological Considerations of Optical Interfaces for Neuromodulation

Biological Considerations of Optical Interfaces for Neuromodulation

Neuromodulation of metabolic functions: from pharmaceuticals to bioelectronics to biocircuits

Nanoscale Patterning of In Vitro Neuronal Circuits

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