<p>Ischemic stroke, induced by the occlusion of cerebral blood vessels, represents a leading cause of global morbidity and mortality. Although thrombolytic therapy and mechanical thrombectomy are cornerstone treatments for restoring cerebral perfusion, their clinical effectiveness is severely constrained by a narrow therapeutic window. This study presents a reactive oxygen species (ROS) - responsive hydrogel platform loaded with engineered apoptotic vesicles (apoVs) designed to simultaneously target multiple post-stroke pathological processes. Proteomic analyses reveal that apoV isolated from apoptotic neural stem cells are enriched in proteins associated with angiogenesis and neuroprotection. In vitro investigations and in vivo animal experiment further demonstrate that the hydrogel can alleviate oxidative stress, promote angiogenesis and protect nerve injury by releasing hydrogen sulfide (H₂S) - functionalized apoV in the infarct area. In summary, this hydrogel platform holds considerable therapeutic promise by transforming the hostile post-stroke microenvironment into a regeneration-permissive niche, thereby fostering endogenous tissue repair.</p> Graphical Abstract <p></p>