Effects of mechanical stimuli on bone cells for regenerative medicine: A review of recent experimental and computational methods

Abstract

Mechanobiology integrates biological and mechanical cues to provide a comprehensive understanding of how physical forces influence tissue regeneration, specifically focusing on bone growth and repair. This review presents a comprehensive overview of the latest developments in bone mechanobiology and highlights the remaining scientific and methodological challenges. Following a brief presentation of the challenges facing cell therapy, and in particular the application of different types of mechanical stimuli, the article examines these various processes on cells and tissues such as compressors and bioreactors operating at low frequencies (in the Hz range). Special attention is given to cutting-edge ultrasound techniques, such as the LIPUS method with MHz frequencies and low intensities ranging from 0.5 to 100 mW/cm², and with an emphasis on the emerging application of acoustic levitation with frequencies ranging from 340 kHz to 2.12 MHz permitting non-invasive manipulation of cells and tissues in biological research, with initial beneficial results in cell therapy. Lastly, the review offers a detailed analysis of multi-scale and multi-physics in silico approaches that may contribute to interpret the obtained experimental results. Agent-based models capture the discrete behaviour of individual cells, while continuum models describe tissue mechanics though averaged properties, offering complementary approaches to study complex mechanobiological phenomena. Such approaches hold the potential to drive transformative advances in bone regeneration medicine, providing a roadmap for future research.