Engineered Extracellular Vesicles Target Ephrinb2 Delivery For Pulp Vascular Regeneration

Traditional root canal therapy cannot restore pulp functionality. This study engineered Apt02-targeted extracellular vesicles (B2-EVs-Apt) to enhance vascular regeneration in dental pulp. Ethics-approved human dental pulp stem cells (DPSCs) were used. EphrinB2-loaded EVs (B2-EVs) and Apt02-modified EVs (B2-EVs-Apt) were developed via ultracentrifugation and chemical conjugation. In vitro (HUVECs) and in vivo (nude mice subcutaneous models) assessments included proliferation (CCK-8), migration (scratch/Transwell), angiogenesis (Matrigel), and GelMA-hydrogel delivery. Data were analyzed by t-test/ANOVA (P<0.05). B2-EVs-Apt achieved 34.4% EphrinB2 encapsulation and >90% aptamer binding, significantly boosting endothelial cell functions (P<0.05) and activating Akt/ERK1/2/EphB4 pathways. In vivo, B2-EVs-Apt@GelMA generated dense vascular networks with elevated VEGF and microvessel density (P<0.01 vs. controls). Targeted EVs synergistically drive angiogenesis via dual signaling activation, providing a breakthrough strategy for functional dental pulp regeneration.