Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, 200001, China.
Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China.
J Nanobiotechnology. 2024 Apr 4;22(1):150. doi: 10.1186/s12951-024-02393-9.
Dental pulp regeneration is a promising strategy for addressing tooth disorders. Incorporating this strategy involves the fundamental challenge of establishing functional vascular networks using dental pulp stem cells (DPSCs) to support tissue regeneration. Current therapeutic approaches lack efficient and stable methods for activating DPSCs. In the study, we used a chemically modified microRNA (miRNA)-loaded tetrahedral-framework nucleic acid nanostructure to promote DPSC-mediated angiogenesis and dental pulp regeneration. Incorporating chemically modified miR-126-3p into tetrahedral DNA nanostructures (miR@TDNs) represents a notable advancement in the stability and efficacy of miRNA delivery into DPSCs. These nanostructures enhanced DPSC proliferation, migration, and upregulated angiogenesis-related genes, enhancing their paracrine signaling effects on endothelial cells. This enhanced effect was substantiated by improvements in endothelial cell tube formation, migration, and gene expression. Moreover, in vivo investigations employing matrigel plug assays and ectopic dental pulp transplantation confirmed the potential of miR@TDNs in promoting angiogenesis and facilitating dental pulp regeneration. Our findings demonstrated the potential of chemically modified miRNA-loaded nucleic acid nanostructures in enhancing DPSC-mediated angiogenesis and supporting dental pulp regeneration. These results highlighted the promising role of chemically modified nucleic acid-based delivery systems as therapeutic agents in regenerative dentistry and tissue engineering.
牙髓再生是一种有前途的策略，可用于解决牙齿疾病。将该策略应用于临床涉及到一个基本挑战，即利用牙髓干细胞（DPSCs）建立功能性血管网络，以支持组织再生。目前的治疗方法缺乏激活 DPSCs 的有效且稳定的方法。在研究中，我们使用化学修饰的 microRNA（miRNA）负载的四面体框架核酸纳米结构来促进 DPSC 介导的血管生成和牙髓再生。将化学修饰的 miR-126-3p 整合到四面体 DNA 纳米结构（miR@TDNs）中，是提高 miRNA 递送至 DPSCs 的稳定性和功效的显著进展。这些纳米结构增强了 DPSCs 的增殖、迁移，并上调了与血管生成相关的基因，增强了它们对内皮细胞的旁分泌信号作用。内皮细胞管形成、迁移和基因表达的改善证实了这种增强作用。此外，体内实验通过使用基质胶塞实验和异位牙髓移植证实了 miR@TDNs 在促进血管生成和促进牙髓再生方面的潜力。我们的研究结果表明，化学修饰的负载 miRNA 的核酸纳米结构在增强 DPSC 介导的血管生成和支持牙髓再生方面具有潜力。这些结果突出了化学修饰的基于核酸的递药系统作为再生医学和组织工程中治疗剂的有前途的作用。
