Local delivery and controlled release of miR-34a loaded in hydroxyapatite/ mesoporous organosilica nanoparticles composite-coated implant wire to accelerate bone fracture healing
Local delivery and controlled release of miR-34a loaded in hydroxyapatite/ mesoporous organosilica nanoparticles composite-coated implant wire to accelerate bone fracture healing
复制标题
羟基磷灰石/介孔有机二氧化硅纳米粒子复合涂层植入线中装载的 miR-34a 的局部递送和控制释放加速骨折愈合
DOI：
10.1016/j.biomaterials.2021.121300
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发表时间：
2022-01-01
期刊：
影响因子：
14
通讯作者：
Chen, Yu
中科院分区：
文献类型：
--
作者：
Guo, Xiang;Xue, Mintao;Chen, Yu
即刻的机械稳定性是骨折愈合的先决条件。除了为骨折部位带来即时的机械稳定性外，具有生物活性涂层的植入物还可以释放活性物质来加速骨折愈合。然而，有限的载药能力，建立涂层削弱了他们的生物功能，这促使工程更有效的涂层生物材料，以加速骨折愈合。在本文中，将介孔有机二氧化硅纳米颗粒（MON）（如miR-34 a递送的）加载到羟基磷灰石（HA）涂覆的克氏针上以设计HA/MONs@miR-34 a复合涂层。该复合涂层可以有效地将miR-34 a递送到破骨细胞中，通过调节骨折愈合早期多个下游基因的表达，对破骨细胞的分化和吸收活性产生基因剂量依赖性抑制作用，并表现出良好的骨再生潜力，正如大鼠胫骨骨折模型所证明的那样。具体而言，使用RNA-seq随后进行生物信息学分析来鉴定由miR-34 a调控的差异表达基因。功能富集分析显示，表达改变的基因主要分布在与破骨细胞发育相关的DNA复制和细胞周期中。这项工作不仅证明了HA/ MONs@miR-34 a在促进骨折愈合方面的高临床翻译潜力，而且基于对erce ell RNA测序的分析揭示了调节破骨细胞生理功能的潜在分子机制。
Immediate mechanical stability is a prerequisite for fracture healing. In addition to bringing immediate me-chanical stability in fracture site, implants with bioactive coating can release active substance to accelerate bone-fracture healing. However, limited drug-loading capacity of established coatings weakens their biological functions, which urges the engineering of more effective coating biomaterials for accelerating fracture healing. Herein, mesoporous organosilica nanoparticles (MONs), as miR-34a delivers, are loaded onto hydroxyapatite (HA)-coated Kirschner wire to engineer a HA/MONs@miR-34a composite coating. The composite coating can effectively deliver miR-34a into osteoclasts, generate gene dose-dependent inhibiting effect on differentiation and resorptive activity of osteoclasts by regulating multiple downstream gene expression at the early stage of fracture healing, which additionally exhibits decent bone regeneration potentials as evidenced in rat tibial fracture model. In particular, differentially expressed genes regulated by miR-34a are identified using RNA-seq followed by bioinformatics analysis. Functional enrichment analysis reveals that genes with altered expression mainly distribute in mainly distribute in DNA replication and cell cycle, which are associated with the devel-opment of osteoclasts. This work not only demonstrates the high clinical translation potential of HA/ MONs@miR-34a to accelerate fracture healing, but also reveals the underlying molecular mechanism of regu-lating physiological functions of osteoclasts based on analysis of singlecell RNA sequencing.