Biophysical stimuli for promoting bone repair and regeneration

Bone injuries and diseases are associated with profound changes in the biophysical properties of living bone tissues, particularly their electrical and mechanical properties. The biophysical properties of healthy bone are attributed to the complex network of interactions between its various cell types (i.e., osteocytes, osteoclast, immune cells and vascular endothelial cells) with the surrounding extracellular matrix (ECM) against the backdrop of a myriad of biomechanical and bioelectrical stimuli arising from daily physical activities. Understanding the pathophysiological changes in bone biophysical properties is critical to developing new therapeutic strategies and novel scaffold biomaterials for orthopedic surgery and tissue engineering, as well as provides a basis for the application of various biophysical stimuli as therapeutic agents to restore the physiological microenvironment of injured/diseased bone tissue, to facilitate its repair and regeneration. These include mechanical, electrical, magnetic, thermal and ultrasound stimuli, which will be critically examined in this review. A significant advantage of utilizing such biophysical stimuli to facilitate bone healing is that these may be applied non-invasively with minimal damage to surrounding tissues, unlike conventional orthopedic surgical procedures. Furthermore, the effects of such biophysical stimuli can be localized specifically at the bone defect site, unlike drugs or growth factors that tend to diffuse away after delivery, which may result in detrimental side effects at ectopic sites.