ArticleJournal of nanobiotechnology2026
Dual-engineered extracellular vesicles enabling endothelial targeting and EphrinB2 delivery for pulp revascularization.
Article in Journal of nanobiotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Dental pulp pathologies impair quality of life and systemic health. Obstacles to revascularization remain a key challenge in regenerating dental pulp tissue. To address these challenges, dual-engineered extracellular vesicles (EVs) were developed, incorporating EphrinB2 as a pro-regenerative payload alongside the DNA aptamer Apt02 for endothelial-targeting specificity. This study identified 1 µg/mL as the optimal concentration for fabricating EphrinB2-loaded extracellular vesicles (B2-EVs). At this concentration, B2-EVs significantly enhanced the proliferation, migration, and capillary morphogenesis of HUVECs. Subsequent integration of the endothelial-targeting Apt02 yielded Apt-B2-EVs, which demonstrated superior affinity for HUVECs and amplified pro-angiogenic capacity. Mechanistic analyses confirmed that Apt-B2-EVs promote angiogenesis via the EphrinB2/EphB4-dependent Akt/ERK signaling cascade. These vesicles were further encapsulated within methacrylated gelatin (GelMA) hydrogel, exhibiting sustained release kinetics and excellent biocompatibility. Implantation of Apt-B2-EVs@GelMA into root canals established pulp organoids, which, upon ectopic transplantation in nude mice, robustly enhanced vascularization. The dual-engineered Apt-B2-EVs present a potent strategy for recruiting endothelial cells and delivering EphrinB2 to enable functional pulp revascularization within root canal niches, laying a translational foundation for next-generation functional pulp regeneration.
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