Therapeutic ultrasound: development of a low-intensity ultrasound stimulator for bone cells

Context
Bone tissue is a complex biological tissue, capable of adapting to its mechanical environment by optimizing its structure, a process called bone remodeling. Low-intensity ultrasound (LIUS) stimulation of bone regeneration was discovered in the 1950s and has been widely studied ever since. However, the underlying mechanotransduction mechanisms (translation of mechanical stimuli into biological response) remain poorly identified and this lack of knowledge fuels controversy, preventing the development of efficient and optimized therapeutic tools. The characterization and quantification of mechanical stresses induced by LIUS stimulation on bone cells are essential to understand these mechanisms. To gain insight into this multiscale and multiphysic phenomena, the development of in vitro studies on cell culture dishes is a key step. A first in vitro experimental device has been developed and tested on 2D cell cultures (i.e., inside cell culture dishes). This LIUS-stimulator enables serial cell cultures to be stimulated in a fully automated way, inside an incubator (simultaneous processing of up to 20 (5×4) independent cell culture dishes), while controlling the acoustic dose delivered to the cells.

Objectives
The objectives of the proposal are to
1 – improve the serial LIUS stimulator to make it more flexible to use and more ergonomic
2 – optimize acoustic conditions for 2D and 3D cell cultures: ultrasonic field and intensity control,
3 – integrate live imaging of LIUS effects in 2D and 3D cell cultures

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