Abstract
Cerebrovascular accidents and spinal cord injuries are the leading cause of paralysis.While full restoration of motor functions is yet unattainable, partial recovery is madepossible thanks to electrical stimulation : as of today, this approach is already improvingthe quality of life of paralyzed patients and restoring partial independence. Electricalstimulation consists in exciting biological tissues with an electrical current to elicita physiological or a motor response. In particular, functional electrical stimulationfocuses on restoring motor function in neuromuscular disorders. However, modernimplants still have flaws that limit chronic use.Electrical stimulation does not faithfully mimic the function of the neuromuscularsystem : particularly, it does not follow the natural order of recruitment of muscle fibers.Instead, it activates the largest and most-fatigable fibers first, leading to prematuremuscle fatigue. Currently, most electrical stimulation devices operate in open-loop,meaning their stimulation parameters are preprogrammed and do no adjust withrespect to the physiological state of the stimulated tissues (i.e. their fatigue). Thislack of adaptability greatly hinders the efficacy of the system, as well as its long-termusability. This matter motivates the development of closed-loop controlled systems,that will monitor the efficacy of stimulation and adapt their parameters with respect tomuscle fatigue. As a complex, multifactorial, and dynamic phenomenon, muscle fatiguetranslates to diverse physiological, metabolic, mechanical, and electrical alterations.In turn, these affect the passive electrical properties of muscle tissues (conductivity,permittivity), which can be evaluated through bioimpedance measurements.The goal of this thesis is to establish a marker of electrically-induced muscle fatigue.This marker should objectively evaluate the physiological state of muscle tissue andthe efficiency of stimulation. To that end, we use bioimpedance measurements thatevaluate the intrinsic electrical properties of tissue and encode their physiologicalstate. Bioimpedance is a fast electrical measurement, performed thanks to electrodesthat already exist in electrostimulation systems. In this work, we seek to identify abioimpedance-based marker of muscle fatigue on an in vitro skeletal muscle cell model,chosen for its simplicity and rapid deployment towards a proof-of-concept. This thesismanuscript describes our investigations and findings in :• Developing and characterizing two in vitro skeletal muscle models, one in 2D (onmicroelectrode arrays) and the other 3D (muscle organoids cultured on PDMSpillars, closer to in vivo conditions). In the latter, the equipment responsible forboth electrical stimulation of 3D muscle tissue and measurement of contractionforce was validated.• Developing and validating the instrumentation responsible for electrical stimulationand bioimpedance measurements on the in vitro cell models.• Deploying a proof-of-concept of bioimpedance-based measurements of musclefatigue on in vitro 2D muscle cells.Through several stimulation scenarios, we demonstrate that the developed systemis capable of inducing muscle cell activity on an in vitro 2D model that further leadsto measurable effects on bioimpedance. Conclusions are drawn from the measuredbioimpedance variations observed with respect to stimulation patterns, in order tovalidate the ability of bioimpedance to reflect muscle fatigue. From the groundspresented in this thesis, future works will aim at extending the results to the 3D invitro cell model developed at the end of the thesis.