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

作者：Castano Irene Mencia; Curtin Caroline M; Shaw Georgina; Murphy J Mary; Duffy Garry P^*; O'Brien Fergal J

来源：Journal of Controlled Release, 2015, 200: 42-51.

DOI：10.1016/j.jconrel.2014.12.034

• MicroRNA
• Nanohydroxyapatite particles
• Collagen-based scaffolds
• Human mesenchymal stem cells
• Tissue engineering

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.

• 出版日期2015-2-28