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<p>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&#xa0;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.</p> Graphical Abstract <p></p>

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Dual-engineered extracellular vesicles enabling endothelial targeting and EphrinB2 delivery for pulp revascularization

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月30日

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  • Anqi Liu,
  • Mengying Li,
  • Peiyu Tang,
  • Weiwen Ge,
  • Zhengliang Han,
  • Yige Dai,
  • Lei Zhang,
  • Changyong Yuan,
  • Lei Qi

摘要

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.

Graphical Abstract