Functional neurological restoration of amputated peripheral nerve using biohybrid regenerative bioelectronics

Rochford, Amy E.; Carnicer‐Lombarte, Alejandro; Kawan, Malak; Jin, Amy; Hilton, Sam; Curto, Vincenzo F.; Rutz, Alexandra L.; Moreau, Thomas; Kotter, Mark R.; Malliaras, George G.; Barone, Damiano G.

doi:10.1126/sciadv.add8162

Cited by 30 publications

(19 citation statements)

References 33 publications

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“…It exhibited remarkable nerve cell integration and signal enhancement properties in a rat model, which is expected to provide a potential therapeutic prospect for amputees and paralyzed patients. [274] Recently, a new method for dynamically constructing flexible conductive materials without substrate in vivo for neural interfaces has been reported. An injectable gel precursor system was designed to be injected into biological tissues, followed by the enzyme polymerization of the precursor in the gel to form a CPH with long-distance conductivity, resulting in a near-seamless interface.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Challenges and Opportunities of Implantable Neural Interfaces: From Material, Electrochemical and Biological Perspectives

Zeng

Huang

2023

Adv Funct Materials

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The desirable implantable neural interfaces can accurately record bioelectrical signals from neurons and regulate neural activities with high spatial/time resolution, facilitating the understanding of neuronal functions and dynamics. However, the electrochemical performance (impedance, charge storage/injection capacity) is limited with the miniaturization and integration of neural electrodes. The “crosstalk” caused by the uneven distribution of elctric field leads to lower electrical stimulation/recording efficiency. The mismatch between stiff electrodes and soft tissues exacerbates the inflammatory responses, thus weakening the transmission of signals. Though remarkable breakthroughs have been made through the incorporation of optimizing electrode design and functionalized nanomaterials, the chronic stability, and long‐term activity in vivo of the neural electrodes still need further development. In this review, the neural interface challenges mainly on electrochemistry and biology are discussed, followed by summarizing typical electrode optimization technologies and exploring recent advances in the application of nanomaterials, based on traditional metallic materials, emerging 2D materials, conducting polymer hydrogels, etc., for enhancing neural interfaces. The strategies for improving the durability including enhanced adhesion and minimized inflammatory response, are also summarized. The promising directions are finally presented to provide enlightenment for high‐performance neural interfaces in future, which will promote profound progress in neuroscience research.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Challenges and Opportunities of Implantable Neural Interfaces: From Material, Electrochemical and Biological Perspectives

Zeng

Huang

2023

Adv Funct Materials

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“…An interface that affords low fouling is always needed to break the boundary between electronic devices and living tissues. Driven by this need, Rochford et al developed a novel type of neural interface that has a layer of human induced pluripotent stem cell (iPSC)-derived myocytes grafted onto flexible CP electrode arrays (Figure A and B) . Such a cell layer acted as the biological target for the peripheral nerve to deliver signals and also provided intimate and biocompatible contacts between the electrodes and the nerves (Figure C).…”

Section: Implantable Biosensorsmentioning

confidence: 99%

“…(G) Images of immunofluorescence stains of biohybrid (bottom) and control devices (top) for axons (β3-tubulin, green) and NMJs (AChE, magenta), as well as cell nuclei (DAPI, gray) 28 days postimplantation. Reproduced with permission from ref . Copyright 2023, American Association for the Advancement of Science.…”

Section: Implantable Biosensorsmentioning

confidence: 99%

“…Surface modifications have been used to achieve intimate and compatible interfaces, but there is yet more to be investigated. Moving forward from chemical functionalization to biofunctionalizations, conjugation of biomolecules (e.g., proteins or growth factors), use of biomimetic hydrogels and even incorporation of living cell layers, are of great potential in improving the biointerfacing properties of soft electrodes. , …”

Section: Summary and Future Prospectsmentioning

confidence: 99%

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Electrochemical and Electrical Biosensors for Wearable and Implantable Electronics Based on Conducting Polymers and Carbon-Based Materials

Zhang,

Zhu,

et al. 2023

Chem. Rev.

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Bioelectronic devices are designed to translate biological information into electrical signals and vice versa, thereby bridging the gap between the living biological world and electronic systems. Among different types of bioelectronics devices, wearable and implantable biosensors are particularly important as they offer access to the physiological and biochemical activities of tissues and organs, which is significant in diagnosing and researching various medical conditions. Organic conducting and semiconducting materials, including conducting polymers (CPs) and graphene and carbon nanotubes (CNTs), are some of the most promising candidates for wearable and implantable biosensors. Their unique electrical, electrochemical, and mechanical properties bring new possibilities to bioelectronics that could not be realized by utilizing metals-or silicon-based analogues. The use of organic-and carbon-based conductors in the development of wearable and implantable biosensors has emerged as a rapidly growing research field, with remarkable progress being made in recent years. The use of such materials addresses the issue of mismatched properties between biological tissues and electronic devices, as well as the improvement in the accuracy and fidelity of the transferred information. In this review, we highlight the most recent advances in this field and provide insights into organic and carbon-based (semi)conducting materials' properties and relate these to their applications in wearable/implantable biosensors. We also provide a perspective on the promising potential and exciting future developments of wearable/implantable biosensors.

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“…Next-generation approaches to achieving flexible brain–computer interfaces and neurological diagnostics require microfabrication or nanomaterials to enable a comfortable bridge between implantable devices and the feeble human brain. − Flexible neural interfaces with high comfortability and minimal invasiveness may promote the long-term recording of neural activity, leading to advances in neuroscientific studies. − In addition, flexible neural interfaces may introduce transformative changes in diagnosis and therapies for peripheral disease by electrical stimulation. − However, the enormous mechanical mismatch between rigid implantable devices and soft brain tissues inevitably causes damage and inflammatory response. , Therefore, stretchable biodevices with mechanically compliant living brain tissue are desired for long-term implantation and signal recording. , Developing stretchable interfaces with superior mechanical properties can deform soft brain tissues and fully record neural activity under long-term active environments. , …”

Section: Introductionmentioning

confidence: 99%

Stretchable, Self-Rolled, Microfluidic Electronics Enable Conformable Neural Interfaces of Brain and Vagus Neuromodulation

Dong,

Wang,

et al. 2024

ACS Nano

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Implantable neuroelectronic interfaces have gained significant importance in long-term brain−computer interfacing and neuroscience therapy. However, due to the mechanical and geometrical mismatches between the electrode−nerve interfaces, personalized and compatible neural interfaces remain serious issues for peripheral neuromodulation. This study introduces the stretchable and flexible electronics class as a self-rolled neural interface for neurological diagnosis and modulation. These stretchable electronics are made from liquid metal−polymer conductors with a high resolution of 30 μm using microfluidic printing technology. They exhibit high conformability and stretchability (over 600% strain) during body movements and have good biocompatibility during long-term implantation (over 8 weeks). These stretchable electronics offer real-time monitoring of epileptiform activities with excellent conformability to soft brain tissue. The study also develops self-rolled microfluidic electrodes that tightly wind the deforming nerves with minimal constraint (160 μm in diameter). The in vivo signal recording of the vagus and sciatic nerve demonstrates the potential of self-rolled cuff electrodes for sciatic and vagus neural modulation by recording action potential and reducing heart rate. The findings of this study suggest that the robust, easy-to-use self-rolled microfluidic electrodes may provide useful tools for compatible neuroelectronics and neural modulation.

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Functional neurological restoration of amputated peripheral nerve using biohybrid regenerative bioelectronics

Cited by 30 publications

References 33 publications

Challenges and Opportunities of Implantable Neural Interfaces: From Material, Electrochemical and Biological Perspectives

Challenges and Opportunities of Implantable Neural Interfaces: From Material, Electrochemical and Biological Perspectives

Electrochemical and Electrical Biosensors for Wearable and Implantable Electronics Based on Conducting Polymers and Carbon-Based Materials

Stretchable, Self-Rolled, Microfluidic Electronics Enable Conformable Neural Interfaces of Brain and Vagus Neuromodulation

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