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A promising approach to treat patients with vocal fold paralysis using electrical stimulation is investigated throughout this research work. Functional Electrical Stimulation works by stimulating the atrophied muscle or group of muscles directly by current when the transmission lines between the central nervous system are disrupted. This technique helps maintain muscle mass and promote blood flow in the absence of a functioning nervous system. The goal of this work is two-fold: develop control techniques for muscle contraction to optimize muscle stimulation and develop a small-scale electromagnetic system to provide stimulation to the laryngeal muscles for patients with vocal fold paralysis. These studies; therefore, focus on assessing a linear Proportional-Integral (PI) controller and two nonlinear controllers: Model Reference Adaptive Controller (MRAC) and an Adaptive Augmented PI (ADP-PI) system to identify the most appropriate controller providing effective stimulation of the muscle. Direct stimulation is applied to mouse skeletal muscle in vitro to test the controllers along with numerical simulations for validation of these experimental tests. The experiments included muscle contractions following four distinct trajectories: a step, sine, ramp, and square wave. Overall, the closed-loop controllers followed the stimulation trajectories set for all the simulated and tested muscles. When comparing the experimental outcomes of each controller, we concluded that the ADP-PI algorithm provided the best closed-loop performance for speed of convergence and disturbance rejection. Next, the focus of the research work was on the implementation of an electromagnetic system to generate appropriate currents of stimulation using the aforementioned controllers. For this study, Nickel-Titanium shape memory alloys were used to assess activation (contraction) through a two-coil system guided by the controllers. The application of the two-coil system demonstrated the effectiveness of the approach and a main effect was observed between the PI, MRAC, and ADP-PI controllers when following the trajectories. Lastly, a small scale two-coil system is developed for animal testing in the muscle-mass-spring setup. Experiments were successful in generating the appropriate stimulation controlled by the output-based algorithms for muscle contraction. Trials conducted for this study were compared to the muscle contractions observed in the first study. The controllers were able to provide appropriate stimulation to the muscle system to follow the set trajectories: a step, ramp, and sinusoidal input. More trials are required to draw statistical conclusions about the performance of each controller. Regardless, the small-scale two-coil system along with the applied controllers can be reconfigured to be an implantable system and tested for appropriate stimulation of the laryngeal muscles. / Ph. D.

Yes / Mesenchymal stem cells (MSCs) are multipotent adult stem cells with great potential in regenerative medicine. One method for stimulating proliferation and differentiation of MSCs is via electrical stimulation (ES). A valuable approach for evaluating the response of MSCs to ES is to assess changes in gene expression, relative to one or more reference genes. In a survey of 25 publications that used ES on cells, 70% selected GAPDH as the reference gene. We conducted a study to assess the suitability of six potential reference genes on an immortalized human MSC line following direct current ES at seeding densities of 5000 and 10,000 cells/cm2 . We employed three methods to validate the most stable reference genes from qRT-PCR data. Our findings show that GAPDH and ACTB exhibit reduced stability when seeded at 5000 cell/cm2 . In contrast, we found that the most stable genes across both plating densities and stimulation regimes were PPIA and YWHAZ. Thus, in ES gene expression studies in MSCs, we support the use of PPIA and YWHAZ as an optimal reference gene pair, and discourage the use of ACTB and GAPDH at lower seeding densities. However, it is strongly recommended that similar verification studies are carried out based on cell type and different ES conditions.

Spinal cord injury and stroke affect many people each year and can result in the loss of muscle function. Current research attempts to correct muscle paralysis through the use of mechanical braces or through open-loop stimulation methods. However, prosthetic systems that use closed-loop control strategies can offer improved functionality by accounting for the changing dynamics associated with the human body and external disturbances. In particular, closed-loop functional electrical stimulation (FES) offers the possibility of moving paralyzed muscles in a predetermined manner, allowing a paraplegic individual to regain the ability to perform some tasks. An experimental setup was designed for the development and testing of a closed-loop FES control system, as well as the characterization of muscle properties. Due to the complexities associated with using a human subject, an inverted pendulum model is utilized for this preliminary study. This model is a basic engineering control problem often used when studying postural control in humans. In particular, electrical stimuli will be applied to the gastrocnemius muscle of a frog in order to produce a contraction force that will drive an inverted pendulum and maintain its desired angle. The stimulation signal will be determined by control algorithms applied through the use of Matlab® and implemented in real-time with a data acquisition system. This setup will help provide an understanding of the muscle behavior and can be used to establish the validity of proposed controller methods.