Advanced small extracellular vesicles delivery systems for in situ tissue engineering

In situ tissue engineering, which activates the body's innate regenerative capacity, has demonstrated superior clinical translation potential than traditional ex situ approaches. Small extracellular vesicles (sEVs), as natural nanovesicles, can excellently mimic the paracrine functions of cells and are thus emerging as promising cell-free alternatives for in situ tissue engineering. Despite advantages such as low immunogenicity, multi-target regulatory capabilities, and cross biological barriers availability, the therapeutic sustainability of sEVs is limited by their rapid clearance in vivo, underscoring the need for effective delivery systems. This review systematically summarizes the sources and bioactivities of sEVs, delineates the design principles and technological advances in sEVs delivery systems, and highlights their application in tissue engineering, while also outlining future trajectories for the development of intelligent delivery platforms.