The relationship between glial cell mechanosensitivity and foreign body reactions in the central nervous system

Moshayedi, Pouria; Ng, Gilbert; Kwok, Jerry; Yeo, Giles S.H.; Bryant, Clare E.; Fawcett, James W.; Franze, Kristian; Guck, Jochen

doi:10.1016/j.biomaterials.2014.01.038

Cited by 333 publications

(340 citation statements)

References 31 publications

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“…All the rats with stiff implants displayed significant deformation of spinal segments under the implant (p < 0.001, We then visualized neuro-inflammatory responses at chronic stages using antibodies against activated astrocytes and microglia (Fig. 2C), two standard cellular markers for foreign body reaction (12). As anticipated from macroscopic damage, both cell types massively accumulated in the vicinity of stiff implants (p < 0.05, Fig.…”

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confidence: 90%

Electronic dura mater for long-term multimodal neural interfaces

Minev

Musienko

Hirsch

et al. 2015

Science

889

925

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Abstract:We introduce a new class of neural implants with the topology and compliance of dura mater, the protective membrane of the brain and spinal cord. These neural interfaces, which we called e-dura, achieve chronic bio-integration within the subdural space where they conform to the statics and dynamics of neural tissue. e-dura embeds interconnects, electrodes and chemotrodes that sustain millions of mechanical stretch cycles, electrical stimulation pulses, and chemical injections. These integrated modalities enable multiple neuroprosthetic applications. e-dura extracted cortical states in freely behaving animals for brain machine interface, and delivered electrochemical spinal neuromodulation that restored locomotion after paralyzing spinal cord injury. e-dura offers a novel platform for chronic multimodal neural interfaces in basic research and neuroprosthetics.3 Neuroprosthetic medicine is improving the lives of countless individuals. Cochlear implants restore hearing in deaf children, deep brain stimulation alleviates Parkinsonian symptoms, and spinal cord neuromodulation attenuates chronic neuropathic pain (1). These interventions rely on implants developed in the 1980s (2, 3). Since then, advances in electroceutical, pharmaceutical, and more recently optogenetic treatments triggered development of myriad neural interfaces that combine multiple modalities (4-9). However, the conversion of these sophisticated technologies into chronic implants mediating long-lasting functional benefits has yet to be achieved. A recurring challenge restricting chronic bio-integration is the substantial biomechanical mismatch between implants and neural tissues (10-13). Here, we introduce a new class of soft multimodal neural interfaces that achieve chronic bio-integration, and we demonstrate their long-term efficacy in clinically relevant applications. e-dura fabrication. We designed and engineered soft interfaces that mimic the topology and mechanical behavior of the dura mater (Fig. 1A-B). The implant, which we called electronic dura mater or e-dura, integrates a transparent silicone substrate (120µm in thickness), stretchable gold interconnects (35nm in thickness), soft electrodes coated with a novel platinum-silicone composite (300µm in diameter), and a compliant fluidic microchannel (100µm x 50µm in crosssection) (Fig. 1C-D, fig. S1-S2-S3). The interconnects and electrodes transmit electrical excitation and transfer electrophysiological signals.The microfluidic channel, termed chemotrode (14), delivers drugs locally (Fig. 1C, fig. S3). Microcracks in the gold interconnects (15) and the newly developed soft platinum-silicone composite electrodes confer exceptional stretchability to the entire implant (Fig. 1B, Movie S1). The patterning techniques of metallization and microfluidics support rapid manufacturing of customized neuroprostheses.4 e-dura implantation. Most implants used experimentally or clinically to assess and treat neurological disorders are placed above the dura mater (3,(16)(17)(18). The compliance of e-...

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mentioning

confidence: 90%

Electronic dura mater for long-term multimodal neural interfaces

Minev

Musienko

Hirsch

et al. 2015

Science

889

925

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“…One obvious approach to pacify cells in contact with an implant seems to be the use of materials with the same bulk modulus as CNS tissue. ▶ As a proof of concept, implantation of (non-electrically functional) soft hydrogel stripes (with an elastic modulus of 100 Pa) caused less FBR than stripes of the same mat erial that were two orders of magnitude stiffer 102 (FIG. 5c).…”

Section: Engineering the Local Mechanical Microenvironmentmentioning

confidence: 99%

“…It is increasingly appreciated that neurons and glial cells respond to the mechanical properties of their surroundings 23,100 : neurons prefer softer regions over stiffer regions for growth and branching 101 ; oligodendrocytes have an optimal stiffness of about 700 Pa (Young's modulus) for growth, proliferation, migration and differentiation 35 ; astrocytes and microglia become activated on stiff surfaces 102 ; and microglia migrate to regions that are stiffer (that is, with a Young's modulus >10 kPa) 103 . One obvious approach to pacify cells in contact with an implant seems to be the use of materials with the same bulk modulus as CNS tissue.…”

Section: Engineering the Local Mechanical Microenvironmentmentioning

confidence: 99%

Materials and technologies for soft implantable neuroprostheses

2016

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| Implantable neuroprostheses are engineered systems designed to restore or substitute function for individuals with neurological deficits or disabilities. These systems involve at least one uni-or bidirectional interface between a living neural tissue and a synthetic structure, through which information in the form of electrons, ions or photons flows. Despite a few notable exceptions, the clinical dissemination of implantable neuroprostheses remains limited, because many implants display inconsistent long-term stability and performance, and are ultimately rejected by the body. Intensive research is currently being conducted to untangle the complex interplay of failure mechanisms. In this Review, we emphasize the importance of minimizing the physical and mechanical mismatch between neural tissues and implantable interfaces. We explore possible materials solutions to design and manufacture neurointegrated prostheses, and outline their immense therapeutic potential. NATURE REVIEWS | MATERIALSADVANCE ONLINE PUBLICATION | 1 REVIEWS© 2 0 1 6 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .

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“…In general, advances in the modulation and recording of neural activities have spurred the development of a myriad of implantable neuroprostheses. Nevertheless, to date, the long-term biointegration and the anticipated therapeutic benefits of these neural implants have not materialized owing to the significant biomechanical mismatch between the stiff implantable neuroprostheses and the soft neural tissues 120,121 . Consequently, Minev et al exploited soft neurotechnology in tailoring their e-dura implants.…”

Section: Therapeutic and Drug-delivery Platformsmentioning

confidence: 99%

Emerging flexible and wearable physical sensing platforms for healthcare and biomedical applications

2016

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There are now numerous emerging flexible and wearable sensing technologies that can perform a myriad of physical and physiological measurements. Rapid advances in developing and implementing such sensors in the last several years have demonstrated the growing significance and potential utility of this unique class of sensing platforms. Applications include wearable consumer electronics, soft robotics, medical prosthetics, electronic skin, and health monitoring. In this review, we provide a state-ofthe-art overview of the emerging flexible and wearable sensing platforms for healthcare and biomedical applications. We first introduce the selection of flexible and stretchable materials and the fabrication of sensors based on these materials. We then compare the different solid-state and liquid-state physical sensing platforms and examine the mechanical deformation-based working mechanisms of these sensors. We also highlight some of the exciting applications of flexible and wearable physical sensors in emerging healthcare and biomedical applications, in particular for artificial electronic skins, physiological health monitoring and assessment, and therapeutic and drug delivery. Finally, we conclude this review by offering some insight into the challenges and opportunities facing this field.

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The relationship between glial cell mechanosensitivity and foreign body reactions in the central nervous system

Cited by 333 publications

References 31 publications

Electronic dura mater for long-term multimodal neural interfaces

Electronic dura mater for long-term multimodal neural interfaces

Materials and technologies for soft implantable neuroprostheses

Emerging flexible and wearable physical sensing platforms for healthcare and biomedical applications

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