Multifunctional peptide-conjugated nanocarriers for pulp regeneration in a full-length human tooth root.
Multifunctional peptide-conjugated nanocarriers for pulp regeneration in a full-length human tooth root.
复制标题
用于全长人牙根牙髓再生的多功能肽缀合纳米载体。
DOI：
10.1016/j.actbio.2021.03.059
复制
发表时间：
2021-06
影响因子：
9.7
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Li Q;Hu Z;Liang Y;Xu C;Hong Y;Liu X
牙髓是一种高度血管化的组织，位于被刚性牙本质壁包围的不可扩展的环境中。牙髓的血液供应完全来自牙根的小根尖孔。由于全长牙根独特的解剖结构控制着营养供应，牙髓组织的再生一直是再生牙髓学的一个挑战。在这项研究中，我们设计并合成了一个多功能肽偶联的、ph敏感的、非病毒基因载体，用于全长人牙根的快速血供重建和牙髓再生。多功能肽被设计成具有独特的特征，包括一个细胞穿透肽，以增强细胞摄取，一个核定位信号肽，以协助血管生成基因易位到细胞核，以及一个荧光色氨酸残基，以可视化和量化转染效率。此外，将ph敏感的二甲基马来酸酐（DMA）与多功能肽结合，增强转染的基因复合物在内化后从核内体/溶酶体中逃逸。体外实验表明，该多功能非病毒基因载体显著提高了内化和基因转染效率，降低了细胞毒性。将多功能基因载体/pVEGF复合物转染牙髓干细胞（DPSCs）后，DPSCs中VEGF的表达上调了8倍以上，从而大大促进了内皮细胞的迁移和血管样管的形成。植入6周后，vegf转染的DPSCs加速了新血管的形成，再生的牙髓组织占据了全长人牙根管的大部分面积。多功能肽偶联非病毒基因传递是一种安全有效的再生牙髓治疗方法。
Dental pulp is a highly vascularized tissue, situated in an inextensible environment surrounded by rigid dentinal walls. The pulp receives its blood supply solely from the small apical foramen of a tooth root. Due to the unique anatomy that controls nutrition supply, regeneration of pulp tissue in a full-length tooth root has long been a challenge in regenerative endodontics. In this study, we designed and synthesized a multifunctional peptide-conjugated, pH-sensitive, non-viral gene vector for fast revascularization and pulp regeneration in a full-length human tooth root. The multifunctional peptide was designed to have distinctive features, including a cell-penetrating peptide to enhance cellular uptake, a nuclear localization signal peptide to assist in the translocation of an angiogenic gene into the nucleus, and a fluorescent tryptophan residue to visualize and quantify the transfection efficiency. Furthermore, a pH-sensitive dimethylmaleic anhydride (DMA) was integrated with the multifunctional peptide to enhance the transfected gene complex to escape from endosomes/lysosomes after internalization. In vitro experiments showed that the multifunctional non-viral gene vector significantly increased internalization and gene transfection efficiency as well as reduced cytotoxicity. After dental pulp stem cells (DPSCs) were transfected with the multifunctional gene vector/pVEGF complexes, the expression of VEGF from the DPSCs was upregulated for more than eight folds, which in turn greatly enhanced endothelial cell migration and vascular-like tube formation. Six weeks after implantation, the VEGF-transfected DPSCs accelerated new blood vessel formation and the regenerated pulp tissue occupied most of the area in the canal of a full-length human tooth root. The multifunctional peptide conjugated non-viral gene delivery is a safe and effective approach for regenerative endodontics.
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影响因子：
3.7
作者：
Bronckaers A;Hilkens P;Fanton Y;Struys T;Gervois P;Politis C;Martens W;Lambrichts I
通讯作者：
Lambrichts I
通过调节仿生基质的硬度来完成牙髓牙本质复合物的再生。
影响因子：
9.7
作者：
Qu, Tiejun;Jing, Junjun;Liu, Xiaohua
通讯作者：
Liu, Xiaohua
影响因子：
9.7
作者：
Chen, Kang;Guo, Lingling;Chen, Dawei
通讯作者：
Chen, Dawei
影响因子：
4.1
作者：
Galler, Kerstin M.;Hartgerink, Jeffrey D.;D'Souza, Rena N.
通讯作者：
D'Souza, Rena N.
影响因子：
4.2
作者：
Della Peruta, Marco;Badar, Adam;Nathwani, Amit C.
通讯作者：
Nathwani, Amit C.