Chemically modified microRNA delivery via DNA tetrahedral frameworks for dental pulp regeneration

Abstract 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 la...

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Main Authors: Xiaoling Wei, Huaxing Xu, Mengqi Zhou, Qiangqiang Zhou, Mingqiang Li, Yuehua Liu
Format: Article
Language:English
Published: BMC 2024-04-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-024-02393-9
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author Xiaoling Wei
Huaxing Xu
Mengqi Zhou
Qiangqiang Zhou
Mingqiang Li
Yuehua Liu
author_facet Xiaoling Wei
Huaxing Xu
Mengqi Zhou
Qiangqiang Zhou
Mingqiang Li
Yuehua Liu
author_sort Xiaoling Wei
collection DOAJ
description Abstract 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. Graphical abstract
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spelling doaj.art-0621c507d2064267a4c85947a05fb28d2024-04-07T11:29:14ZengBMCJournal of Nanobiotechnology1477-31552024-04-0122111810.1186/s12951-024-02393-9Chemically modified microRNA delivery via DNA tetrahedral frameworks for dental pulp regenerationXiaoling Wei0Huaxing Xu1Mengqi Zhou2Qiangqiang Zhou3Mingqiang Li4Yuehua Liu5Shanghai Stomatological Hospital and School of Stomatology, Fudan UniversityShanghai Stomatological Hospital and School of Stomatology, Fudan UniversityShanghai Stomatological Hospital and School of Stomatology, Fudan UniversityShanghai Stomatological Hospital and School of Stomatology, Fudan UniversitySchool of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, National Center for Translational Medicine, Shanghai Jiao Tong UniversityShanghai Stomatological Hospital and School of Stomatology, Fudan UniversityAbstract 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. Graphical abstracthttps://doi.org/10.1186/s12951-024-02393-9Dental pulp regenerationDental pulp stem cellsAngiogenesisNucleic acid modificationsTetrahedral-framework nucleic acid nanostructure
spellingShingle Xiaoling Wei
Huaxing Xu
Mengqi Zhou
Qiangqiang Zhou
Mingqiang Li
Yuehua Liu
Chemically modified microRNA delivery via DNA tetrahedral frameworks for dental pulp regeneration
Journal of Nanobiotechnology
Dental pulp regeneration
Dental pulp stem cells
Angiogenesis
Nucleic acid modifications
Tetrahedral-framework nucleic acid nanostructure
title Chemically modified microRNA delivery via DNA tetrahedral frameworks for dental pulp regeneration
title_full Chemically modified microRNA delivery via DNA tetrahedral frameworks for dental pulp regeneration
title_fullStr Chemically modified microRNA delivery via DNA tetrahedral frameworks for dental pulp regeneration
title_full_unstemmed Chemically modified microRNA delivery via DNA tetrahedral frameworks for dental pulp regeneration
title_short Chemically modified microRNA delivery via DNA tetrahedral frameworks for dental pulp regeneration
title_sort chemically modified microrna delivery via dna tetrahedral frameworks for dental pulp regeneration
topic Dental pulp regeneration
Dental pulp stem cells
Angiogenesis
Nucleic acid modifications
Tetrahedral-framework nucleic acid nanostructure
url https://doi.org/10.1186/s12951-024-02393-9
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AT huaxingxu chemicallymodifiedmicrornadeliveryviadnatetrahedralframeworksfordentalpulpregeneration
AT mengqizhou chemicallymodifiedmicrornadeliveryviadnatetrahedralframeworksfordentalpulpregeneration
AT qiangqiangzhou chemicallymodifiedmicrornadeliveryviadnatetrahedralframeworksfordentalpulpregeneration
AT mingqiangli chemicallymodifiedmicrornadeliveryviadnatetrahedralframeworksfordentalpulpregeneration
AT yuehualiu chemicallymodifiedmicrornadeliveryviadnatetrahedralframeworksfordentalpulpregeneration