Stem cell-derived extracellular vesicles for high-altitude skin injuries: pathological mechanisms, advanced...

The extreme high-altitude environment-characterized by hypobaric hypoxia, intense ultraviolet radiation, and severe cold and aridity-imposes complex physical and biochemical stresses that synergistically drive pronounced cutaneous oxidative stress and barrier collapse. Given the limited capacity of conventional interventions to restore damaged cutaneous microenvironments, stem cell-derived extracellular vesicles (SC-EVs) have emerged as a promising cell-free regenerative modality for multitarget intervention. By delivering a diverse repertoire of bioactive molecules, SC-EVs concurrently help restore reactive oxygen species (ROS) homeostasis, attenuate inflammatory cascades, modulate angiogenesis, and mitigate extracellular matrix (ECM) degradation, thereby promoting coordinated restoration of cutaneous homeostasis. Nevertheless, the rapid in vivo clearance and limited structural stability of native EVs severely bottleneck their clinical translation. To surmount these limitations, advanced nanodelivery platforms-such as stimuli-responsive hydrogels and liposomal hybrids-may provide strategies to improve the targeted spatial retention, spatiotemporal release, and overall bioavailability of EVs. This review systematically summarizes and discusses the molecular mechanisms by which SC-EVs counteract composite high-altitude skin injuries. By bridging cutting-edge nanodelivery technologies with altitude-specific therapeutic adaptations, we delineate a potential translational framework for developing non-invasive nanotherapeutics tailored for the precise prevention and treatment of high-altitude dermatological damage.