Description of the thesis topic

Bone is a biological material that is sensitive to mechanical stimuli. The cells involved in bone balance can convert the mechanical signals received into biological signals to maintain a bone architecture that provides mechanical support to our body adapted to the physiological loads it is subjected to. This mechanosensitivity therefore appears to be a key biological mechanism that must be considered when developing a care strategy. For example, an implant with specific mechanical properties will modify the mechanical environment felt by the cells and therefore influence their activities. In this context, the current regulations allowing the transfer of a care product to the clinic imply the use of animal models to subject the product to the most physiological environment possible. While these models raise ethical and societal issues, they remain essential due to the lack of alternatives. The purpose of this thesis project is to develop an experimental device to provide complementary data on bone mechanosensitivity and thus delay the use of animals.
The device will allow to apply a mechanical loading to a bone sample while tracking markers of mechanical stimulation at the scale of the cells trapped within bone architecture. In particular, the project will focus on a type of cell playing a key role in bone mechanobiology: the osteocyte. These cells are entangled in an interconnected porous network, composed of lacunae, in which the osteocytes are housed, connected to each other by submicrometric canaliculi. Through bone poroelasticity, the deformation of bone matrix induces pressure gradients with a consequent variation in the velocity and pressure of the fluids flowing in this network. This variation in the fluidic behavior within the lacunocanalicular network is considered to be the mechanical signal sensed by osteocytes. This signal is then converted into biological mediators to the bony vascular channels where osteoclasts and osteoblasts are located in charge of bone resorption and formation, respectively. It therefore seems relevant to understand how mechanical loading applied at the scale of the bone sample influences the circulation of fluids in this lacunocanalicular network. A first step will be to test the device developed on bone samples to set up markers to monitor the perfusion of the lacunocanalicular network.
In a second phase, bone samples harvested during orthopedic surgeries will be recovered in collaboration with the HCL. These samples will be kept alive and subjected to mechanical loading within the device to assess its influence on the evolution of bone properties.
This work will therefore lead to a better understanding of the mechanisms of mechanical stimulation of osteocytes and their influence on the cellular response; Additionally, the new experimental device will appear as an alternative experimental model to animal experimentation providing complementary insights on bone mechanobiology. This thesis project is integrated into a global project in which numerical models, twin of the experimental set-up, will be developed in parallel to provide new elements of understanding on the circulation of fluids within the bone porous network during loading. Thus, many dialogues between the candidate will be expected with the team in charge of the numerical model (coord. Thibault Lemaire, MSME).
The candidate must hold an engineering degree and/or a master's degree in mechanics and/or materials science. Skills in mechanical design and instrumentation will be a plus to set up the experimental set-up. An attraction to biological experimentation is essential. Good oral and written skills are essential for communication and the valorization of the scientific results obtained throughout the thesis.

Work Context

This thesis project is part of the ANR BoNoBio project (ANR-25-CE51-7990) involving 5 laboratories at the national level:
- MatéIS UMR 5510 (CNRS – INSA Lyon – UCBL) (coordinator)
- LaMCoS UMR 5259 (CNRS – INSA Lyon)
- LMI UMR 5615 (CNRS – UCBL)
- LCMCP UMR 7574 (CNRS – Sorbonne Universities – Collège de France)
- MSME UMR 8208 (CNRS – Univ. Gustave Eiffel – UPEC)
The thesis will take place straddling the MatéIS laboratories, a Materials Science laboratory at the intersection of disciplinary fields, mainly in chemistry, physics and mechanics, and LaMCoS, which aims to conduct research on the mastery and control of the behavior of mechanical systems and structures by taking into account their interfaces. The thesis will be co-supervised by Rémy Gauthier (CR CNRS, MatéIS) and Ana-Maria Trunfio-Sfarghiu (DR CNRS, LaMCoS). Regular interactions will be carried out with the other actors of the BoNoBio project.

The position is located in a sector under the protection of scientific and technical potential (PPST), and therefore requires, in accordance with the regulations, that your arrival is authorized by the competent authority of the MESR.