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  • 1
    Online Resource
    Online Resource
    In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice
    Wiley ; 2020
    In:  Journal of Neuroscience Research Vol. 98, No. 10 ( 2020-10), p. 2072-2095
    Details
    In: Journal of Neuroscience Research, Wiley, Vol. 98, No. 10 ( 2020-10), p. 2072-2095
    Abstract: Electrical stimulation has been critical in the development of an understanding of brain function and disease. Despite its widespread use and obvious clinical potential, the mechanisms governing stimulation in the cortex remain largely unexplored in the context of pulse parameters. Modeling studies have suggested that modulation of stimulation pulse waveform may be able to control the probability of neuronal activation to selectively stimulate either cell bodies or passing fibers depending on the leading polarity. Thus, asymmetric waveforms with equal charge per phase (i.e., increasing the leading phase duration and proportionately decreasing the amplitude) may be able to activate a more spatially localized or distributed population of neurons if the leading phase is cathodic or anodic, respectively. Here, we use two‐photon and mesoscale calcium imaging of GCaMP6s expressed in excitatory pyramidal neurons of male mice to investigate the role of pulse polarity and waveform asymmetry on the spatiotemporal properties of direct neuronal activation with 10‐Hz electrical stimulation. We demonstrate that increasing cathodic asymmetry effectively reduces neuronal activation and results in a more spatially localized subpopulation of activated neurons without sacrificing the density of activated neurons around the electrode. Conversely, increasing anodic asymmetry increases the spatial spread of activation and highly resembles spatiotemporal calcium activity induced by conventional symmetric cathodic stimulation. These results suggest that stimulation polarity and asymmetry can be used to modulate the spatiotemporal dynamics of neuronal activity thus increasing the effective parameter space of electrical stimulation to restore sensation and study circuit dynamics.
    Type of Medium: Online Resource
    ISSN: 0360-4012 , 1097-4547
    URL: Issue
    URL: Article
    DOI: 10.1002/jnr.v98.10
    DOI: 10.1002/jnr.24676
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 1474904-X
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Hierarchically aligned fibrous hydrogel films through microfluidic self‐assembly of graphene and polysaccharides
    Wiley ; 2018
    In:  Biotechnology and Bioengineering Vol. 115, No. 10 ( 2018-10), p. 2654-2667
    Details
    In: Biotechnology and Bioengineering, Wiley, Vol. 115, No. 10 ( 2018-10), p. 2654-2667
    Abstract: Despite significant interest in developing extracellular matrix (ECM)‐inspired biomaterials to recreate native cell‐instructive microenvironments, the major challenge in the biomaterial field is to recapitulate the complex structural and biophysical features of native ECM. These biophysical features include multiscale hierarchy, electrical conductivity, optimum wettability, and mechanical properties. These features are critical to the design of cell‐instructive biomaterials for bioengineering applications such as skeletal muscle tissue engineering. In this study, we used a custom‐designed film fabrication assembly, which consists of a microfluidic chamber to allow electrostatic charge‐based self‐assembly of oppositely charged polymer solutions forming a hydrogel fiber and eventually, a nanocomposite fibrous hydrogel film. The film recapitulates unidirectional hierarchical fibrous structure along with the conductive properties to guide initial alignment and myotube formation from cultured myoblasts. We combined high conductivity, and charge carrier mobility of graphene with biocompatibility of polysaccharides to develop graphene–polysaccharide nanocomposite fibrous hydrogel films. The incorporation of graphene in fibrous hydrogel films enhanced their wettability, electrical conductivity, tensile strength, and toughness without significantly altering their elastic properties (Young's modulus). In a proof‐of‐concept study, the mouse myoblast cells (C2C12) seeded on these nanocomposite fibrous hydrogel films showed improved spreading and enhanced myogenesis as evident by the formation of multinucleated myotubes, an early indicator of myogenesis. Overall, graphene–polysaccharide nanocomposite fibrous hydrogel films provide a potential biomaterial to promote skeletal muscle tissue regeneration.
    Type of Medium: Online Resource
    ISSN: 0006-3592 , 1097-0290
    URL: Issue
    URL: Article
    DOI: 10.1002/bit.v115.10
    DOI: 10.1002/bit.26801
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 1480809-2
    detail.hit.zdb_id: 280318-5
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    A Materials Roadmap to Functional Neural Interface Design
    Wiley ; 2018
    In:  Advanced Functional Materials Vol. 28, No. 12 ( 2018-03)
    Details
    In: Advanced Functional Materials, Wiley, Vol. 28, No. 12 ( 2018-03)
    Abstract: Advancements in neurotechnologies for electrophysiology, neurochemical sensing, neuromodulation, and optogenetics are revolutionizing scientific understanding of the brain while enabling treatments and preventative measures for a variety of neurological disorders. The grand challenge in neural interface engineering is to seamlessly integrate the interface between neurobiology and engineered technology to record from and modulate neurons over chronic timescales. However, the biological inflammatory response to implants, neural degeneration, and long‐term material stability diminishes the quality of the interface overtime. Recent advances in functional materials are aimed at engineering solutions for chronic neural interfaces, yet, the development and deployment of neural interfaces designed from novel materials have introduced new challenges that have been largely unaddressed. Many engineering efforts that solely focus on optimizing individual probe design parameters, such as softness or flexibility, downplay critical multidimensional interactions between different physical properties of the device that contribute to overall performance and biocompatibility. Moreover, the use of these new materials present substantial new difficulties that must be addressed before regulatory approval for use in human patients is achievable. In this review, the interdependence of different electrode components is highlighted to demonstrate the current material‐based challenges facing the field of neural interface engineering.
    Type of Medium: Online Resource
    ISSN: 1616-301X , 1616-3028
    URL: Issue
    URL: Article
    DOI: 10.1002/adfm.v28.12
    DOI: 10.1002/adfm.201701269
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2029061-5
    detail.hit.zdb_id: 2039420-2
    SSG: 11
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  • 4
    Online Resource
    Online Resource
    Calcium activation of cortical neurons by continuous electrical stimulation: Frequency dependence, temporal fidelity, and activation density
    Wiley ; 2019
    In:  Journal of Neuroscience Research Vol. 97, No. 5 ( 2019-05), p. 620-638
    Details
    In: Journal of Neuroscience Research, Wiley, Vol. 97, No. 5 ( 2019-05), p. 620-638
    Abstract: Electrical stimulation of the brain has become a mainstay of fundamental neuroscience research and an increasingly prevalent clinical therapy. Despite decades of use in basic neuroscience research and the growing prevalence of neuromodulation therapies, gaps in knowledge regarding activation or inactivation of neural elements over time have limited its ability to adequately interpret evoked downstream responses or fine‐tune stimulation parameters to focus on desired responses. In this work, in vivo two‐photon microscopy was used to image neuronal calcium activity in layer 2/3 neurons of somatosensory cortex (S1) in male C57BL/6J‐Tg(Thy1‐GCaMP6s)GP4.3Dkim/J mice during 30 s of continuous electrical stimulation at varying frequencies. We show frequency–dependent differences in spatial and temporal somatic responses during continuous stimulation. Our results elucidate conflicting results from prior studies reporting either dense spherical activation of somas biased toward those near the electrode, or sparse activation of somas at a distance via axons near the electrode. These findings indicate that the neural element specific temporal response local to the stimulating electrode changes as a function of applied charge density and frequency. These temporal responses need to be considered to properly interpret downstream circuit responses or determining mechanisms of action in basic science experiments or clinical therapeutic applications.
    Type of Medium: Online Resource
    ISSN: 0360-4012 , 1097-4547
    URL: Issue
    URL: Article
    DOI: 10.1002/jnr.v97.5
    DOI: 10.1002/jnr.24370
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1474904-X
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Zwitterionic Polymer Coating Suppresses Microglial Encapsulation to Neural Implants In Vitro and In Vivo
    Wiley ; 2020
    In:  Advanced Biosystems Vol. 4, No. 6 ( 2020-06)
    Details
    In: Advanced Biosystems, Wiley, Vol. 4, No. 6 ( 2020-06)
    Abstract: For brain computer interfaces (BCI), the immune response to implanted electrodes is a major biological cause of device failure. Bioactive coatings such as neural adhesion molecule L1 have been shown to improve the biocompatibility, but are difficult to handle or produce in batches. Here, a synthetic zwitterionic polymer coating, poly(sulfobetaine methacrylate) (PSBMA) is developed for neural implants with the goal of reducing the inflammatory host response. In tests in vitro, the zwitterionic coating inhibits protein adsorption and the attachment of fibroblasts and microglia, and remains stable for at least 4 weeks. In vivo two‐photon microscopy on CX3CR1‐GFP mice shows that the zwitterionic coating significantly suppresses the microglial encapsulation of neural microelectrodes over a 6 h observation period. Furthermore, the lower microglial encapsulation on zwitterionic polymer‐coated microelectrodes is revealed to originate from a reduction in the size but not the number of microglial end feet. This work provides a facile method for coating neural implants with zwitterionic polymers and illustrates the initial interaction between microglia and coated surface at high temporal and spatial resolution.
    Type of Medium: Online Resource
    ISSN: 2366-7478 , 2366-7478
    URL: Issue
    URL: Article
    DOI: 10.1002/adbi.v4.6
    DOI: 10.1002/adbi.201900287
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2880980-4
    detail.hit.zdb_id: 3027224-5
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