Significance of mechanical loading in bone fracture healing, bone regeneration, and vascularization

In 1892, J.L. Wolff proposed that bone could respond to mechanical and biophysical stimuli as a dynamic organ. This theory presents a unique opportunity for investigations on bone and its potential to aid in tissue repair. Routine activities such as exercise or machinery application can exert mechanical loads on bone. Previous research has demonstrated that mechanical loading can affect the differentiation and development of mesenchymal tissue. However, the extent to which mechanical stimulation can help repair or generate bone tissue and the related mechanisms remain unclear. Four key cell types in bone tissue, including osteoblasts, osteoclasts, bone lining cells, and osteocytes, play critical roles in responding to mechanical stimuli, while other cell lineages such as myocytes, platelets, fibroblasts, endothelial cells, and chondrocytes also exhibit mechanosensitivity. Mechanical loading can regulate the biological functions of bone tissue through the mechanosensor of bone cells intraosseously, making it a potential target for fracture healing and bone regeneration. This review aims to clarify these issues and explain bone remodeling, structure dynamics, and mechano-transduction processes in response to mechanical loading. Loading of different magnitudes, frequencies, and types, such as dynamic versus static loads, are analyzed to determine the effects of mechanical stimulation on bone tissue structure and cellular function. Finally, the importance of vascularization in nutrient supply for bone healing and regeneration was further discussed.