Mechanically remodeled extracellular vesicles: drivers of disease or therapeutic opportunities?

Mechanical signals contribute to tissue homeostasis and disease progression by regulating cell behavior and intercellular communication. Extracellular vesicles (EVs) can relay donor-cell responses to mechanical stimuli to recipient cells, linking the mechanical microenvironment to physiological and pathological changes. Drawing on 98 studies published between January 2015 and February 2026, this review examines the connections between mechanical stimulation, EV remodeling and biological outcomes. We outline the mechanisms linking cellular mechanosensing and mechanotransduction to EV biogenesis, release and molecular remodeling, alongside changes in EV abundance, size, cargo, and function. We then discuss how these changes shape EV activity under conditions of physiological homeostasis, adaptive stress and pathological loading. Mechanically remodeled EVs can support homeostasis and tissue repair or promote disease progression, depending on the stimulus characteristics and the environments of donor and recipient cells. Beyond their local and distant effects, EVs may also contribute to feedback regulation of mechanical responses. Such feedback may involve direct effects on donor cells or changes in the local microenvironment mediated by neighboring cells. These proposed mechanisms require further direct experimental support. By connecting mechanical inputs with EV remodeling and function, this Review offers a framework for understanding intercellular communication within the mechanical microenvironment. It also considers implications for optimizing therapeutic EV production and exploring interventions in disease.