Delivery of antagomiR204-conjugated gold nanoparticles from PLGA sheets and its implication in promoting osseointegration of titanium implant in type 2 diabetes mellitus.
Delivery of antagomiR204-conjugated gold nanoparticles from PLGA sheets and its implication in promoting osseointegration of titanium implant in type 2 diabetes mellitus.
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从 PLGA 片递送 antagomiR204 缀合的金纳米粒子及其对促进 2 型糖尿病钛种植体骨整合的意义
DOI：
10.2147/ijn.s124584
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发表时间：
2017
影响因子：
8
通讯作者：
Song Y
中科院分区：
文献类型：
--
作者：
Liu X;Tan N;Zhou Y;Wei H;Ren S;Yu F;Chen H;Jia C;Yang G;Song Y
种植体的骨整合受损仍然是糖尿病患者种植体治疗的一大障碍。在这项研究中，作者首次发现miR204在糖尿病大鼠的骨间充质干细胞（BMSCs）中惊人地高表达。强制表达miR204抑制了骨髓间充质干细胞的成骨潜能，而抑制miR204则显著提高了成骨能力。此外，将miR204抑制剂与金纳米颗粒（AuNP-antagomiR204）偶联，并将其分散在聚乳酸-羟基乙酸（PLGA）溶液中。采用含有PLGA溶液的AuNP-antagomiR204包覆钛种植体表面。电镜观察发现，植入体表面形成超薄层，AuNPs均匀分布在包覆的PLGA薄片上。细胞实验表明，这些包封的AuNP-antagomiR204能够从PLGA薄片上释放出来，并被粘附的骨髓间充质干细胞吸收。体内动物实验进一步证实，PLGA薄片释放的AuNP-antagomiR204促进了骨整合，显微ct重建和组织学分析显示。综上所述，本研究确定了miR204的错误表达是糖尿病患者骨整合缺陷的原因，而PLGA薄片有助于AuNP-antagomiR204的释放，这将是一种有希望的钛种植体表面功能化策略，以实现更好的骨整合。
Impaired osseointegration of the implant remains the big hurdle for dental implant therapy in diabetic patients. In this study, the authors first identified that miR204 was strikingly highly expressed in the bone mesenchymal stem cells (BMSCs) of diabetic rats. Forced expression of miR204 repressed the osteogenic potential of BMSCs, while inhibition of miR204 significantly increased the osteogenic capacity. Moreover, the miR204 inhibitor was conjugated with gold nanoparticles (AuNP-antagomiR204) and dispersed them in the poly(lactic-co-glycolic acid) (PLGA) solution. The AuNP-antagomiR204 containing PLGA solution was applied for coating the surface of titanium implant. Electron microscope revealed that an ultrathin sheet was formed on the surface of the implant, and the AuNPs were evenly dispersed in the coated PLGA sheet. Cellular experiments revealed that these encapsulated AuNP-antagomiR204 were able to be released from the PLGA sheet and uptaken by adherent BMSCs. In vivo animal study further confirmed that the AuNP-antagomiR204 released from PLGA sheet promoted osseointegration, as revealed by microcomputerized tomography (microCT) reconstruction and histological assay. Taken together, this study established that miR204 misexpression accounted for the deficient osseointegation in diabetes mellitus, while PLGA sheets aided the release of AuNP-antagomiR204, which would be a promising strategy for titanium implant surface functionalization toward better osseointegration.