Physical Stimulations for Bone and Cartilage Regeneration

A wide range of techniques and methods are actively invented by clinicians and scientists who are dedicated to the field of musculoskeletal tissue regeneration. Biological, chemical, and physiological factors, which play key roles in musculoskeletal tissue development, have been extensively explored. However, physical stimulation is increasingly showing extreme importance in the processes of osteogenic and chondrogenic differentiation, proliferation and maturation through defined dose parameters including mode, frequency, magnitude, and duration of stimuli. Studies have shown manipulation of physical microenvironment is an indispensable strategy for the repair and regeneration of bone and cartilage, and biophysical cues could profoundly promote their regeneration. In this article, we review recent literature on utilization of physical stimulation, such as mechanical forces (cyclic strain, fluid shear stress, etc.), electrical and magnetic fields, ultrasound, shock waves, and substrate stimuli, to promote the repair and regeneration of bone and cartilage tissue. Emphasis is placed on the mechanism of cellular response and the potential clinical usage of these stimulations for bone and cartilage regeneration. Lay Summary Bone and cartilage regenerative engineering aims to create stable, bioactive, and native tissue-like scaffolds which can repair bone and cartilage damages. These scaffolds are often combined with chondrogenic/osteogenic cells or stem cells to create replacement tissue grafts with enhanced regenerative capability. In this approach, physical stimulations such as ultrasound, mechanical force, electrical charge, and magnetic field have significant impacts on cell fate and behavior through regulating various intracellular signaling pathways. The review provides a comprehensive understanding and broad overview of literature on effects of different physical stimulations on cellular behaviors and signaling pathways, which have been reported to induce growth of bone and cartilage. The knowledge lay a strong foundation for the development of future smart tissue grafts that can effectively repair bone and cartilage under physical stimulations. Other future works will focus on combining different physical stimulations and fine-tuning parameters of such stimulations to obtain optimal cartilage and bone regeneration.