A novel collagen-nanohydroxyapatite microRNA-activated scaffold for tissue engineering applications capable of efficient delivery of both miR-mimics and antagomiRs to human mesenchymal stem cells

被引:81
作者
Castano, Irene Mencia [1 ,2 ,3 ]
Curtin, Caroline M. [1 ,2 ,3 ]
Shaw, Georgina [4 ]
Murphy, J. Mary [4 ]
Duffy, Garry P. [1 ,2 ,3 ]
O'Brien, Fergal J. [1 ,2 ,3 ]
机构
[1] Royal Coll Surgeons Ireland, Dept Anat, Tissue Engn Res Grp, Dublin 2, Ireland
[2] Univ Dublin Trinity Coll, Trin Ctr Bioengn, Dublin 2, Ireland
[3] RCSI & TCD, Adv Mat & Bioengn Res AMBER Ctr, Dublin 2, Ireland
[4] Natl Univ Ireland Univ Coll Galway, Regenerat Med Inst, Galway, Ireland
基金
欧洲研究理事会;
关键词
MicroRNA; Nanohydroxyapatite particles; Collagen-based scaffolds; Human mesenchymal stem cells; Tissue engineering; GENE DELIVERY; OSTEOGENIC DIFFERENTIATION; THERAPY; PROLIFERATION; PEPTIDES; MODEL;
D O I
10.1016/j.jconrel.2014.12.034
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Manipulation of gene expression through the use of microRNAs (miRNAs) offers tremendous potential for the field of tissue engineering. However, the lack of sufficient site-specific and bioactive delivery systems has severely hampered the clinical translation of miRNA-based therapies. In this study, we developed a novel non-viral bioactive delivery platform for miRNA mimics and antagomiRs to allow for a vast range of therapeutic applications. By combining nanohydroxyapatite (nHA) particles with reporter miRNAs (nanomiRs) and collagen-nanohydroxyapatite scaffolds, this work introduces the first non-viral, non-lipid platform to date, capable of efficient delivery of mature miRNA molecules to human mesenchymal stem cells (hMSCs), a particularly difficult cell type to transfect effectively, with minimal treatment-associated cytotoxicity. Firstly, miRNAs were successfully delivered to hMSCs in monolayer, with internalisation efficiencies of 17.4 and 39.6% for nanomiR-mimics and nanoantagomiRs respectively, and both nanomiR-mimics and nanoantagomiRs yielded sustained interfering activity of greater than 90% in monolayer over 7 days. When applied to 3D scaffolds, significant RNA interference of 20% for nanomiR-mimics and 88.4% for nanoantagomiRs was achieved with no cytotoxicity issues over a 7 day period. In summary, in-house synthesised non-viral nHA particles efficiently delivered reporter miRNAs both in monolayer and on scaffolds demonstrating the immense potential of this innovative miRNA-activated scaffold system for tissue engineering applications. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:42 / 51
页数:10
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