Using EMG to deliver lumbar dynamic electrical stimulation to facilitate cortico-spinal excitability

Background: Potentiation of synaptic activity in spinal networks is reflected in the magnitude of modulation of motor responses evoked by spinal and cortical input. After spinal cord injury, motor evoked responses can be facilitated by pairing cortical and peripheral nerve stimuli. Objective: To facilitate synaptic potentiation of cortico-spinal input with epidural electrical stimulation, we designed a novel neuromodulation method called dynamic stimulation (DS), using patterns derived from hind limb EMG signal during stepping. Methods: DS was applied dorsally to the lumbar enlargement through a high-density epidural array composed of independent platinum-based micro-electrodes. Results: In fully anesthetized intact adult rats, at the interface array/spinal cord, the temporal and spatial features of DS neuromodulation affected the entire lumbosacral network, particularly the most rostral and caudal segments covered by the array. DS induced a transient (at least 1 min) increase in spinal cord excitability and, compared to tonic stimulation, generated a more robust potentiation of the motor output evoked by single pulses applied to the spinal cord. When sub-threshold pulses were selectively applied to a cortical motor area, EMG responses from the contralateral leg were facilitated by the delivery of DS to the lumbosacral cord. Finally, based on motor-evoked responses, DS was linked to a greater amplitude of motor output shortly after a calibrated spinal cord contusion. Conclusion: Compared to traditional tonic waveforms, DS amplifies both spinal and cortico-spinal input aimed at spinal networks, thus significantly increasing the potential and accelerating the rate of functional recovery after a severe spinal lesion

Adhesion and proliferation of skeletal muscle cells on single layer poly(lactic acid) ultra-thin films

An increasing interest in bio-hybrid systems and cell-material interactions is evident in the last years. This leads towards the development of new nano-structured devices and the assessment of their biocompatibility. In the present study, the development of free-standing single layer poly(lactic acid) (PLA) ultra-thin films is described, together with the analysis of topography and roughness properties. The biocompatibility of the PLA films has been tested in vitro, by seeding C2C12 skeletal muscle cells, and thus assessing cells shape, density and viability after 24, 48 and 72 h. The results show that free-standing flexible PLA nanofilms represent a good matrix for C2C12 cells adhesion, spreading and proliferation. Early differentiation into myotubes is also allowed. The biocompatibility of the novel ultra-thin films as substrates for cell growth promotes their application in the fields of regenerative medicine, muscle tissue engineering, drug delivery, and-in general-in the field of bio-hybrid devices

Acute neuromodulation restores spinally-induced motor responses after severe spinal cord injury

Epidural electrical spinal stimulation can facilitate recovery of volitional motor control in individuals that have been completely paralyzed for more than a year. We recently reported a novel neuromodulation method named Dynamic Stimulation (DS), which short-lastingly increased spinal excitability and generated a robust modulation of locomotor networks in fully-anesthetized intact adult rats. In the present study, we applied repetitive DS patterns to four lumbosacral segments acutely after a contusive injury at lumbar level. Repetitive DS delivery restored the spinally-evoked motor EMG responses that were previously suppressed by a calibrated spinal cord contusion. Sham experiments without DS delivery did not allow any spontaneous recovery. Thus, DS uniquely provides the potential for a greater long-term functional recovery after paralysis

Toward the use of temporary tattoo electrodes for impedancemetric respiration monitoring and other electrophysiological recordings on skin

The development of dry, ultra-conformable and unperceivable temporary tattoo electrodes (TTEs), based on the ink-jet printing of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) on top of commercially available temporary tattoo paper, has gained increasing attention as a new and promising technology for electrophysiological recordings on skin. In this work, we present a TTEs epidermal sensor for real time monitoring of respiration through transthoracic impedance measurements, exploiting a new design, based on the application of soft screen printed Ag ink and magnetic interlink, that guarantees a repositionable, long-term stable and robust interconnection of TTEs with external “docking” devices. The efficiency of the TTE and the proposed interconnection strategy under stretching (up to 10%) and over time (up to 96 h) has been verified on a dedicated experimental setup and on humans, fulfilling the proposed specific application of transthoracic impedance measurements. The proposed approach makes this technology suitable for large-scale production and suitable not only for the specific use case presented, but also for real time monitoring of different bio-electric signals, as demonstrated through specific proof of concept demonstrators

Ultraconformable, Self‐Adhering Surface Electrodes for Measuring Electrical Signals in Plants

The electrical signals in plant's physiological processes are of great interest in biology, biohybrid robotics, and sensors for interfacing the living organisms with an electronic readout and control. This paper reports on the application of conformable, self-adhering surface electrodes for the measurement and bidirectional stimulation of electrical signals in plants. The inkjet-printed poly(3,4-ethylenedioxythiophene) polystyrene sulfonate based electrodes are <3 µm thick, light-weight, soft and flexible, and can be easily and non-invasively transferred onto plant's outer organs for surface potential recordings due to their realization on tattoo transfer paper. The devices prove to be extremely versatile for analyzing electrical signals in Dionaea muscipula, Arabidopsis thaliana, and Codariocalyx motorius and for stimulating mechanical responses in D. muscipula. A benefit over traditional electrodes is the van der Waals self-adherence of the thin electrodes, their intrinsic flexibility and adaptation also on small leaves while providing excellent readout. The same electrode allows long-term multicycle measurements over at least 10 days and, moreover, straightforward recordings on fast-moving organs such as snapping fly traps and endogenously oscillating leaflets. The results confirm that self-adhering soft organic electronics are particularly suitable for plant electrical signal analysis when easy-application, self-adaptation, and long-term performance are required in plant science, biohybrid robotics, and biohybrid sensors

Nanomolar oxytocin synergizes with weak electrical afferent stimulation to activate the locomotor CPG of the rat spinal cord in vitro.

Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks) on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM-1 \u3bcM) generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in combination with other protocols, and delineate the use of oxytocin to strengthen the efficiency of electrical stimulation to activate locomotor circuits

Micro-scale aerosol jet printing of superparamagnetic Fe₃O₄ nanoparticle patterns

The opportunity to create different patterns of magnetic nanoparticles on surfaces is highly desirable across many technological and biomedical applications. In this paper, this ability is demonstrated for the first time using a computer-controlled aerosol jet printing (AJP) technology. AJP is an emerging digitally driven, non-contact and mask-less printing process which has distinguishing advantages over other patterning technologies as it offers high-resolution and versatile direct-write deposition of a wide range of materials onto a variety of substrates. This research demonstrates the ability of AJP to reliably print large-area, fine-feature patterns of superparamagnetic iron oxide nanoparticles (SPIONs) onto both rigid material (glass) and soft and flexible materials (polydimethylsiloxane (PDMS) films and poly-L-lactic acid (PLLA) nanofilms). Investigation identified and controlled influential process variables which permitted feature sizes in the region of 20 μm to be realised. This method could be employed for a wide range of applications that require a flexible and responsive process that permits high yield and rapid patterning of magnetic material over large areas. As a first proof of concept, we present patterned magnetic nanofilms with enhanced manipulability under external magnetic field gradient control and which are capable of performing complex movements such as rotation and bending, with applicability to soft robotics and biomedical engineering applications

Optimization and fabrication of programmable domains for soft magnetic robots: A review

Driven by the aim of realizing functional robotic systems at the milli- and submillimetre scale for biomedical applications, the area of magnetically driven soft devices has received significant recent attention. This has resulted in a new generation of magnetically controlled soft robots with patterns of embedded, programmable domains throughout their structures. This type of programmable magnetic profiling equips magnetic soft robots with shape programmable memory and can be achieved through the distribution of discrete domains (voxels) with variable magnetic densities and magnetization directions. This approach has produced highly compliant, and often bio-inspired structures that are well suited to biomedical applications at small scales, including microfluidic transport and shape-forming surgical catheters. However, to unlock the full potential of magnetic soft robots with improved designs and control, significant challenges remain in their compositional optimization and fabrication. This review considers recent advances and challenges in the interlinked optimization and fabrication aspects of programmable domains within magnetic soft robots. Through a combination of improvements in the computational capacity of novel optimization methods with advances in the resolution, material selection and automation of existing and novel fabrication methods, significant further developments in programmable magnetic soft robots may be realized

A digitally driven manufacturing process for high resolution patterning of cell formations

This paper presents the engineering and validation of an enabling technology that facilitates new capabilities in in vitro cell models for high-throughput screening and tissue engineering applications. This is conducted through a computerized system that allows the design and deposition of high-fidelity microscale patterned coatings that selectively alter the chemical and topographical properties of cell culturing surfaces. Significantly, compared to alternative methods for microscale surface patterning, this is a digitally controlled and automated process thereby allowing scientists to rapidly create and explore an almost infinite range of cell culture patterns. This new capability is experimentally validated across six different cell lines demonstrating how the precise microscale deposition of these patterned coatings can influence spatiotemporal growth and movement of endothelial, fibroblast, neuronal and macrophage cells. To further demonstrate this platform, more complex patterns are then created and shown to guide the behavioral response of colorectal carcinoma cells