Abstract
Skeletal muscle injury during a prolonged stay in intensive care unit is rapid and leads to a decrease in the strenght of the contraction. This weakness affects the diaphragm, the main respiratory muscle, and leads to a delay in weaning from mechanical ventilation and a higher probability of death. In the longer term, weakness to the limbs muscles leads to a poor quality of life and impaired functional autonomy. The main mediator of the persistence of this muscular weakness involves a defect of the muscular regeneration with a quantitative and qualitative impairment of the satellite cells. These translational thesis works had a double objective. The first was to evaluate the feasibility and contribution of shear wave elastography, in order to identify in a non-invasive and early manner a qualitative alteration of the muscles. Through these results, we first demonstrate that the evaluation of shear modulus is feasible and reproducible on a critical patient population. Very good correlation coefficient is obtained for the diaphragm and limbs muscles for two operators. Monitoring the shear modulus (SM) during the SI stay on a cohort of 94 patients allowed us to show that it can decrease or increase, showing a tissue modification. In the mechanically ventilated pig model, MC is associated with a decrease in strength as well as histological damage (muscle fiber atrophy, lipid inclusion). The second objective of this thesis work focused on the development of an in vitro muscle model allowing the study of the muscle regeneration failure. Thanks to the principle of tissue engineering, the first steps of this model were initiated. First of all, and in order to obtain an oriented differentiation of the myotubes in vitro, a new bio-material has been developed to build a microstructured silicone support. This EETMOS-based organic-inorganic hybrid material allows direct and fast microstructuring on silicone by UV laser writing. Moreover, it is a good candidate for use in cell culture: it is non-toxic and has a lower auto-fluorescence than the classical photosensitive material. This work has also demonstrated the feasibility of grafting synthetic peptide onto silicone in association with primary patient cells.