Delivering Multifunctional Peptide-Conjugated Gene Carrier/miRNA-218 Complexes from Monodisperse Microspheres for Bone Regeneration.
Delivering Multifunctional Peptide-Conjugated Gene Carrier/miRNA-218 Complexes from Monodisperse Microspheres for Bone Regeneration.
复制标题
从单分散微球中传递多功能肽偶联的基因载体/miRNA-218复合物以进行骨再生。
DOI：
10.1021/acsami.2c10728
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发表时间：
2022-09-28
影响因子：
9.5
通讯作者：
Liu, Xiaohua
中科院分区：
文献类型：
--
作者：
Li, Qian;Deng, Yuejia;Liu, Xiaohua
microRNAs（miRNAs）在调控基因表达方面起着关键作用，被认为是骨组织工程中的新分子靶点。然而，有效地将miRNAs递送到缺损区域并将miRNAs转染到成骨祖细胞中一直是应用中的障碍。在这项工作中，miRNA-218（miR-218）被用作成骨miRNA调节剂，并且开发了多功能肽缀合的基因载体聚（丙交酯-共-乙交酯）-g-聚乙烯亚胺-b-聚乙二醇-R9-G4-IKVAVW（PPP-RGI），以与miR-218缩合形成PPP-RGI/miR-218复合物，该复合物被进一步包封到单分散可注射微球中以增强骨再生。PPP-RGI通过将多功能肽R9-G4-IKVAVW（RGI）缀合到聚（丙交酯-共-乙交酯-g-聚乙烯亚胺-b-聚乙二醇（PPP））上来合成。进一步开发了微流控和同步光交联工艺以将PPP-RGI/miR-218复合物包封到单分散明胶甲基丙烯酰基微球中。单分散微球控制PPP-RGI/miR-218向指定缺损部位的递送，PPP-RGI促进miR-218转染成骨祖细胞。体内颅骨缺损模型显示，PPP-RGI/miR-218负载微球显著增强骨组织再生。这项工作提供了一种新的方法来有效地提供miRNA和靶向细胞在体内先进的再生疗法。
MicroRNAs (miRNAs) play a pivotal role in regulating gene expression and are considered new molecular targets in bone tissue engineering. However, effective delivery of miRNAs to the defect areas and transfection of the miRNAs into osteogenic progenitor cells has been an obstacle in the application. In this work, miRNA-218 (miR-218) was used as an osteogenic miRNA regulator, and a multifunctional peptide-conjugated gene carrier poly(lactide-co-glycolide)-g-polyethylenimine-b-polyethylene glycol-R9-G4-IKVAVW (PPP-RGI) was developed to condense with miR-218 to form PPP-RGI/miR-218 complexes that were further encapsulated into monodisperse injectable microspheres for enhanced bone regeneration. The PPP-RGI was synthesized via conjugating R9-G4-IKVAVW (RGI), a multifunctional peptide, onto poly(lactide-co-glycolide-g-polyethylenimine-b-polyethylene glycol (PPP). A microfluidic and synchronous photo-cross-linking process was further developed to encapsulate the PPP-RGI/miR-218 complexes into monodisperse gelatin methacryloyl microspheres. The monodisperse microspheres controlled the delivery of PPP-RGI/miR-218 to the designated defect site, and PPP-RGI facilitated the transfection of miR-218 into osteogenic progenitor cells. An in vivo calvarial defect model showed that the PPP-RGI/miR-218-loaded microspheres significantly enhanced bone tissue regeneration. This work provides a novel approach to effectively deliver miRNA and transfect targeting cells in vivo for advanced regenerative therapies.
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影响因子：
3.7
作者：
McCully M;Conde J;V Baptista P;Mullin M;Dalby MJ;Berry CC
通讯作者：
Berry CC
影响因子：
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影响因子：
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通讯作者：
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作者：
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通讯作者：
Khosroushahi AY
DOI：
10.1016/j.msec.2016.09.078
发表时间：
2017-02-01
影响因子：
7.9
作者：
Dozie-Nwachukwu, S. O.;Danyuo, Y.;Soboyejo, W. O.
通讯作者：
Soboyejo, W. O.