Mechano-regulated extracellular vesicles: key mediators in disease pathogenesis and emerging therapeutic avenues.

Extracellular vesicles (EVs) are nanoscale membrane structures secreted by cells and play a key mediating role in intercellular communication. Their biosynthesis and function are profoundly modulated by mechanical signals from the cellular microenvironment. Mechanical forces, including shear stress, tensile strain, and matrix stiffness, exert fundamental effects on cellular behavior and disease progression by regulating the biogenesis, composition, and function of EVs. This review summarizes current knowledge on how biomechanical cues regulate EV-mediated intercellular communication in diseases such as atherosclerosis, osteoarthritis, and cancer. Specifically, we explore the mechanisms by which abnormal mechanical forces alter the cargo of EVs, such as miRNAs, proteins, and lipids, thereby driving disease progression through pathways like plaque instability, metastatic niche formation, and bone metabolism imbalance. Additionally, this review evaluates the therapeutic potential of mechanically regulated EVs, with a focus on their roles as diagnostic biomarkers and targeted drug delivery vehicles. By integrating cutting-edge perspectives from mechanobiology and EV research, this review lays a theoretical foundation for developing novel precision medicine strategies targeting biomechanically driven diseases.