Exoskeleton gait training with spinal cord neuromodulation.

Neuromodulating the locomotor network through spinal cord electrical stimulation (SCES) is effective for restoring function in individuals with gait deficits. However, SCES alone has limited effectiveness without concurrent locomotor function training that enhances activity-dependent plasticity of spinal neuronal networks by sensory feedback. This mini review discusses recent developments in using combined interventions, such as SCES added to exoskeleton gait training (EGT). To develop personalized therapies, it is crucial to assess the state of spinal circuitry through a physiologically relevant approach that identifies individual characteristics of spinal cord function to develop person-specific SCES and EGT. The existing literature suggests that combining SCES and EGT to activate the locomotor network can have a synergistic rehabilitative effect on restoring walking abilities, somatic sensation, and cardiovascular and bladder function in paralyzed individuals.

Exoskeleton Walk Training in Paralyzed Individuals Benefits From Transcutaneous Lumbar Cord Tonic Electrical Stimulation.

In recent years, advanced technologies featuring wearable powered exoskeletons and neuromodulation of lumbosacral spinal networks have been developed to facilitate stepping and promote motor recovery in humans with paralysis. Here we studied a combined effect of spinal cord electrical stimulation (SCES) and exoskeleton walk training (EWT) during an intensive 2-week rehabilitative protocol in spinal cord injury individuals (n = 19, American Spinal Injury Association Impairment Scale (AIS) A-11, B-5, C-3). The purpose of this study was to evaluate the compatibility of methods and to explore the main effects of combined SCES and EWT. All participants had a chronic state of paralysis (1-11 years after trauma). In addition, in the control group (n = 16, AIS A-7, B-5, C-4), we performed EWT without SCES. For EWT, we used a powered exoskeleton (ExoAtlet), while stability was assisted by crutches, with automatic arrest of stepping if excessive torques were detected. SCES was applied to the level of the mid-lumbar cord over the Th12 vertebra at 1 or 3 pulses/s (4 individuals with severe spasticity were also stimulated in an anti-spastic mode 67 pulses/s). The vertical component of the ground reaction force was recorded using the F-Scan system at the onset and after training with SCES. EWT with SCES significantly increased the foot loading forces, could decrease their asymmetry and 8 out of 19 subjects improved their Hauser Ambulation Index. The anti-spastic mode of stimulation also allowed individuals with severe spasticity to walk with the aid of the exoskeleton. Participants reported facilitation when walking with SCES, paresthesia in leg muscles and new non-differential sensation of passive motion in leg joints. Neurological examination showed an increase of tactile (7) and/or pain (7) sensation and an increase of the AIS motor scale in 9 individuals, including both incomplete and complete paralysis. Improvements in the neurological scores were, however, limited in the control group (EWT without SCES). The results suggest that SCES may facilitate training and walking in the exoskeleton by activating the locomotor networks and augmenting compensative sensitivity.

Experimental bladder regeneration using a poly-l-lactide/silk fibroin scaffold seeded with nanoparticle-labeled allogenic bone marrow stromal cells.

In the present study, a poly-l-lactide/silk fibroin (PL-SF) bilayer scaffold seeded with allogenic bone marrow stromal cells (BMSCs) was investigated as a potential approach for bladder tissue engineering in a model of partial bladder wall cystectomy in rabbits. The inner porous layer of the scaffold produced from silk fibroin was designed to promote cell proliferation and the outer layer produced from poly-l-lactic acid to serve as a waterproof barrier. To compare the feasibility and efficacy of BMSC application in the reconstruction of bladder defects, 12 adult male rabbits were divided into experimental and control groups (six animals each) that received a scaffold seeded with BMSCs or an acellular one, respectively. For BMSC tracking in the graft in in vivo studies using magnetic resonance imaging, cells were labeled with superparamagnetic iron oxide nanoparticles. In vitro studies demonstrated high intracellular incorporation of nanoparticles and the absence of a toxic influence on BMSC viability and proliferation. Following implantation of the graft with BMSCs into the bladder, we observed integration of the scaffold with surrounding bladder tissues (as detected by magnetic resonance imaging). During the follow-up period of 12 weeks, labeled BMSCs resided in the implanted scaffold. The functional activity of the reconstructed bladder was confirmed by electromyography. Subsequent histological assay demonstrated enhanced biointegrative properties of the PL-SF scaffold with cells in comparison to the control graft, as related to complete regeneration of the smooth muscle and urothelium tissues in the implant. Confocal microscopy studies confirmed the presence of the superparamagnetic iron oxide nanoparticle-labeled BMSCs in newly formed bladder layers, thus indicating the role of stem cells in bladder regeneration. The results of this study demonstrate that application of a PL-SF scaffold seeded with allogenic BMSCs can enhance biointegration of the graft in vivo and support bladder tissue regeneration and function.