Biomaterials regulates BMSCs differentiation via mechanical microenvironment.

Bone mesenchymal stem cells (BMSCs) are crucial for bone tissue regeneration, the mechanical microenvironment of hard tissues, including bone and teeth, significantly affects the osteogenic differentiation of BMSCs. Biomaterials may mimic the microenvironment of the extracellular matrix and provide mechanical signals to regulate BMSCs differentiation via inducing the secretion of various intracellular factors. Biomaterials direct the differentiation of BMSCs via mechanical signals, including tension, compression, shear, hydrostatic pressure, stiffness, elasticity, and viscoelasticity, which can be transmitted to cells through mechanical signalling pathways. Besides, biomaterials with piezoelectric effects regulate BMSCs differentiation via indirect mechanical signals, such as, electronic signals, which are transformed from mechanical stimuli by piezoelectric biomaterials. Mechanical stimulation facilitates achieving vectored stem cell fate regulation, while understanding the underlying mechanisms remains challenging. Herein, this review summarizes the intracellular factors, including translation factors, epigenetic modifications, and miRNA level, as well as the extracellular factor, including direct and indirect mechanical signals, which regulate the osteogenic differentiation of BMSCs. Besides, this review will also give a comprehensive summary about how mechanical stimuli regulate cellular behaviours, as well as how biomaterials promote the osteogenic differentiation of BMSCs via mechanical microenvironments. The cellular behaviours and activated signal pathways will give more implications for the design of biomaterials with superior properties for bone tissue engineering. Moreover, it will also provide inspiration for the construction of bone organoids which is a useful tool for mimicking in vivo bone tissue microenvironments.