Microfluidic-assisted formulation of cell membrane-camouflaged anisotropic nanostructures.

Anisotropic gold (Au) nanostructures have been widely explored for various nanomedicine applications. While these nanomaterials have shown great promise for disease theranostics, particularly for cancer diagnosis and treatment, the utilization and clinical translation of anisotropic Au nanostructures have been limited by their high phagocytic uptake and clearance and low cancer targeting specificity. Numerous efforts have thus been made toward mitigating these challenges. Many conventional strategies, however, rely on all-synthetic materials, involve complex chemical processes, or have low product throughput and reproducibility. Herein, by integrating cell membrane coating and microfluidic technologies, a high-throughput bioinspired approach for synthesizing biomimetic anisotropic Au nanostructures with minimized phagocytic uptake and improved cancer cell targeting is reported. Through continuous hydrodynamic flow focusing, mixing, and sonication, Au nanostructures are encapsulated within the macrophage and cancer cell membrane vesicles effectively. The fabricated nanostructures are uniform and highly stable in serum. Importantly, the macrophage membrane vesicle-encapsulated Au nanostructures can be preferentially internalized by breast cancer cells, but not by macrophages. Overall, this study has demonstrated the feasibility of employing an integrated microfluidic-sonication technique to formulate uniform and highly stable biomimetic anisotropic nanostructures for enhanced cancer theranostic applications.

Immediate Effects of Functional Electrical Stimulation-Assisted Cycling on the Paretic Muscles of Patients With Hemiparesis After Stroke: Evidence From Electrical Impedance Myography.

Background: Electrical impedance myography (EIM) has been applied to assess muscle health conditions in neuromuscular disorders. This study aimed to detect immediate muscle electrical impedance property alterations in lower extremity of chronic stroke survivors immediately after functional electrical stimulation (FES)-assisted cycling training. Methods: Fourteen chronic stroke survivors were recruited for the current study. EIM measurements were conducted before and immediately after 40-min FES-assisted cycling training for each subject. Four interested muscle groups [rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), and the medial head of gastrocnemius (MG)] were selected. Correlation analysis was performed to reveal a significant correlation between changes in EIM parameters and clinical scales [Fugl-Meyer Assessment of the lower extremity (FMA-LE); 6-min walking test (6MWT)]. Results: Immediately after training, reactance (X) and phase angle (θ) values significantly increased on the TA and MG muscles. Significant correlation was observed between X value and FMA-LE scores (r = 0.649, p = 0.012) at MG as well as X and FMA scores of the ankle joint (r = 0.612, p = 0.02). Resistance (R) and θ were significantly correlated with 6MWT score (R-6MWT: r = 0.651, p = 0.012; θ-6MWT: r = 0.621, p = 0.018). Conclusion: This brief report demonstrated that EIM can reveal the intrinsic property alteration in the paretic muscle of chronic stroke survivors immediately after FES-assisted cycling training. These alterations might be related to muscle hypertrophy (i.e., increases in muscle fiber size). This brief report might aid the understanding of the mechanism of electrical stimulation-assisted exercise in improving muscle function of stroke survivors.

Cortico-muscular interaction to monitor the effects of neuromuscular electrical stimulation pedaling training in chronic stroke.

Neuromuscular electrical stimulation (NMES) has been widely utilized in post-stroke motor restoration. However, its impact on the closed-loop sensorimotor control process remains largely unclear. This is the first study to investigate the directional changes in cortico-muscular interactions after repetitive rehabilitation training by measuring the noninvasive electroencephalogram (EEG) and electromyography (EMG) signals. In this study, 10 subjects with chronic stroke received 20 sessions of NMES-pedaling interventions, and each training session included three 10-min NMES-driven pedaling trials. In addition, pre- and post-intervention assessments of lower limb isometric contraction were conducted before and after the whole NMES-pedaling interventions. The EEG (128 channels) and EMG (3 bilateral lower limb sensors) signals were collected during the isometric contraction tasks for the paretic and non-paretic lower limbs. Both the cortico-muscular coherence (CMC) and generalized partial directed coherence (GPDC) values were analyzed between eight selected EEG channels in the central primary motor cortex and EMG channels. The results revealed significant clinical improvements. Additionally, rehabilitation training facilitated cortico-muscular interaction of the ipsilesional brain and paretic lower limbs (p = 0.004). Moreover, both the descending and ascending cortico-muscular pathways were altered after NMES-training (p = 0.001, p < 0.001). Therefore, the results implied potential applications of EEG-EMG in understanding neuromuscular changes during the post-stroke motor rehabilitation process.

Muscle Electrical Impedance Properties and Activation Alteration After Functional Electrical Stimulation-Assisted Cycling Training for Chronic Stroke Survivors: A Longitudinal Pilot Study.

Electrical impedance myography (EIM) is a sensitive assessment for neuromuscular diseases to detect muscle inherent properties, whereas surface electromyography (sEMG) is a common technique for monitoring muscle activation. However, the application of EIM in detecting training effects on stroke survivors is relatively few. This study aimed to evaluate the muscle inherent properties and muscle activation alteration after functional electrical stimulation (FES)-assisted cycling training to chronic stroke survivors. Fifteen people with chronic stroke were recruited for 20 sessions of FES-assisted cycling training (40 min/session, 3-5 sessions/week). The periodically stimulated and assessed muscle groups were quadriceps (QC), tibialis anterior (TA), hamstrings (HS), and medial head of gastrocnemius (MG) on the paretic lower extremity. EIM parameters [resistance (R), reactance (X), phase angle (θ), and anisotropy ratio (AR)], clinical scales (Fugl-Meyer Lower Extremity (FMA-LE), Berg Balance Scale (BBS), and 6-min walking test (6MWT)] and sEMG parameters [including root-mean square (RMS) and co-contraction index (CI) value] were collected and computed before and after the training. Linear correlation analysis was conducted between EIM and clinical scales as well as between sEMG and clinical scales. The results showed that motor function of the lower extremity, balance, and walking performance of subjects improved after the training. After training, θ value of TA (P = 0.014) and MG (P = 0.017) significantly increased, and AR of X (P = 0.004) value and AR of θ value (P = 0.041) significantly increased on TA. The RMS value of TA decreased (P = 0.022) and a significant reduction of CI was revealed on TA/MG muscle pair (P < 0.001). Significant correlation was found between EIM and clinical assessments (AR of X value of TA and FMA-LE: r = 0.54, P = 0.046; X value of TA and BBS score: 0.628, P = 0.016), and between sEMG and clinical scores (RMS of TA and BBS score: r = -0.582, P = 0.029). This study demonstrated that FES-assisted cycling training improved lower limb function by developing coordinated muscle activation and facilitating an orderly myofiber arrangement. The current study also indicated that EIM can jointly evaluate lower extremity function alteration with sEMG after rehabilitation training. Clinical Trail Registration: The study was registered on the Clinical Trial Registry (trial registration number: NCT03208439, https://clinicaltrials.gov/ct2/show/NCT03208439).

Effects of Electromyographically-driven Neuromuscular Stimulatio Cycling System on the Lower-Limb of Stroke Survivors.

This paper describes the design of an Electromyographically(EMG)-driven Neuromuscular Electrical Stimulation (NMES) cycling system. It utilises real-time EMG from actively participating stroke survivors as feedback control to drive the cycling system for rehabilitation. The user controls the speed of the cycling system using muscle activities of the side affected recorded by EMG electrodes. Additionally, adaptable NMES stimulations; also EMG based, were provided in cyclic pattern to the respective muscle groups in order to improve muscle coordination. The targeted muscle groups used to control the system were the Hamstring (HS), Tibialis Anterior (TA), Quadriceps (QC), Gastrocnemius Lateralis (GL) of the leg on the affected side. Using the system, 20 30-minutes sessions were conducted with chronic stroke survivors (n=10) at frequency of 2-4 sessions per week. Clinical assessment scores, namely FMA_LE, BBS and 6MWT were calculated before the first session and after the completion of 20 sessions. All the assessment scores showed significant improvement after using the system; FMA_LE(P=0.0244), BBS(P=0.0156), 6MWT(P=0.0112), and SI (P=0.0258), showing that the EMG-driven NMES cycling system provides effective rehabilitation for stroke survivors in terms of muscle strength and balance.

Design of Functional Electrical Stimulation Cycling System for Lower-Limb Rehabilitation of Stroke Patients.

The active participation of the stroke survivor during Functional Electrical Stimulation (FES) cycling system is an interesting question that we would like to investigate, since active rehabilitation can promote a better motor function recovery than passive training. In this pilot study, a smart FES cycling system which can assess the participants cycling effort was proposed to record real-time Electromyography (EMG) and torque during lower limb training for chronic stroke survivors. The rehabilitation goals were to increase the lower-limb muscle strength and enhance the muscle coordination. Chronic stroke patients (n=6) with gait impairment and moderate motor disability were recruited to evaluate the functionality of the system. The system was composed of a modified station bike with an adjustable chair, a programmable functional electrical stimulator, a step motor, a torque sensor, and a surface electromyography (EMG) amplifier. Four-channel FES and EMG electrodes were placed at quadriceps (QC), hamstrings (HS), tibialis anterior (TA) and gastrocnemius (GL) to exert stimulation. We adopted two measurements, clinical assessment scores and symmetric index (SI), to evaluate the training effects. The experimental results showed the proposed cycling system could improve the participants walking ability (p=.046) and enhance balance of the muscle coordination (p=.042) after training.

Real-time Electromyography-driven Functional Electrical Stimulation Cycling System for Chronic Stroke Rehabilitation.

Stroke-induced lower extremity dysfunction has become a severe medical problem nowadays and effective rehabilitation methods are in great demand. In this work, a new real-time Electromyography-driven Functional Electrical Stimulation (FES) cycling system was developed to help chronic stroke patients with lower limb rehabilitation training. To evaluate the feasibility and effectiveness of this system, 3 chronic stroke subjects were recruited and each received 20 training sessions where real-time Electromyography (EMG) was used to interact with the cycling system. During the training, two typical metrics, averaged Area Under Torque (AUT) and maximal EMG amplitude, were adopted to measure the muscle strength changes of hamstring (HS). The training results showed that the two measurements of HS both significantly increased, especially the maximal EMG amplitude in the last trial was twice as much as that in the first trial, indicating paretic limb strength increment and functional recovery, which suggested that our system is effective and helpful in the stroke rehabilitation.

How to prepare a person with complete spinal cord injury to use surface electrodes for FES trike cycling.

Functional Electrical Stimulation (FES) cycling could benefit people with Spinal Cord Injury (SCI). The FES cycling involves large muscle groups during the training, and thus improves the cardiovascular function, increases the muscle bulk and reduces the secondary complications. This study developed an outdoor FES exercise cycling system for complete SCI persons to exercise their lower limbs without putting extra load on upper extremities. The mechanical structure of the cycling system was specially redesigned to secure the SCI persons in the cycling system. A six-phase-angle-driven control algorithm was designed to stimulate the quadriceps and hamstrings muscles. Two training modes, i.e., continuous mode and on-off mode, were designed and tested to increase the duration of the electrical stimulation to reduce muscle fatigue. A complete SCI volunteer participated in this training for six months. Beneficial effects could be observed such as paralyzed lower limb muscles had regained the muscle mass and reduced edema from the improved blood circulation. Moreover, the SCI volunteer attended the Cybathlon FES-bike competition in Zurich in October 2016 with Team Phoenix from the CUHK.

The Effectiveness of Functional Electrical Stimulation (FES) in On-Off Mode for Enhancing the Cycling Performance of Team Phoenix at 2016 Cybathlon.

In this study we designed a Functional Electrical Stimulation (FES) trike for a female subject with spinal cord injury to exercise her lower limbs and improve her lower limb muscle condition for attending the 2016 Cybathlon FES bike competition. Our FES pilot was the only female participant, in the FES cycling competition and she rode for Team Phoenix from the Chinese University of Hong Kong. Due to the weakness of muscles in the lower limb of the subject, and due to scoliosis over her thoracolumbar aéra, the mechanical structure of the trike had to be tailor-made to ensure she sat on the bike in a safe and secure position. A six-phase angle-driven stimulation pattern was developed to stimulate quadriceps and hamstrings without gluteus muscles for contraction through four surface electrodes, thereby creating a cycling movement. To improve the cycling endurance and reduce the muscle fatigue, an on-off mode was developed for controlling the stimulation time that allowed the subject to cycle for 20s, then pause while the trike advanced without stimulation for 5s, followed by a subsequent 20 sec stimulation, to continue cycling. The pilot participated in the training procedure including training exercise at home, trike fitting in the trike by modifying the mechanical structure, and conducting the cycling exercise for six months. We observed significant improvements in the pilot's lower limb condition. The on-off mode enabled our pilot to extend her cycling endurance effectively, from 1 min to 2.5 mins and the distance from 62m to 100m. Over the eight minutes time limit, our team successfully finished 100 m in the Cybathlon FES.