Spatiotemporal Delivery of Stem Cell-Derived Extracellular Vesicles for Rapid Wound Healing

Stem cell-derived extracellular vesicles (EVs) have emerged as promising therapeutics for wound healing, yet their clinical applications are limited by rapid clearance and poor retention at wound sites. Conventional delivery systems rely on preformed biomaterials and passive release, which cannot adapt to the dynamic wound environments and provide precise temporal control over EVs availability. Here, we present an in situ forming adhesive hydrogel that enables 405 nm light-triggered gelation at the acute wound surfaces directly and near-infrared (NIR) light-stimulated on-demand release of EVs. This hydrogel integrates EVs within a biocompatible polymer matrix, forming a conformal, shape-adaptable scaffold that can seamlessly cover wounds with irregular geometries. In vitro studies demonstrated NIR-responsive EVs release and preserved bioactivity. In vivo experiments using acute wound models (full-thickness excision and deep second-degree burn) showed dramatically accelerated tissue regeneration, enhanced angiogenesis, and reduced scar formation compared with EVs-only or hydrogel-only treatments. Overall, this work introduces a versatile, multifunctional platform for spatiotemporal EVs delivery, offering new strategies for effective wound repair.