Journal
NATURE COMMUNICATIONS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms10376
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Funding
- US National Institutes of Health [DE015384, DE017689, DE022327, HL114038]
- US National Science Foundation [NSF DMR-1206575]
- Program for Changjiang Scholars and Innovative Research Team in Universities [IRT13051]
- National Natural Science Research Program of China [31501036]
- CSC fellowship from the Chinese Scholarship Council
- School of Stomatology of the Fourth Military Medical University of China
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL114038] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R01DE022327] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [R01DE017689, R01DE015384] Funding Source: NIH RePORTER
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MicroRNAs ( miRNAs) are being developed to enhance tissue regeneration. Here we show that a hyperbranched polymer with high miRNA-binding affinity and negligible cytotoxicity can self-assemble into nano-sized polyplexes with a 'double-shell' miRNA distribution and high transfection efficiency. These polyplexes are encapsulated in biodegradable microspheres to enable controllable two-stage (polyplexes and miRNA) delivery. The microspheres are attached to cell-free nanofibrous polymer scaffolds that spatially control the release of miR-26a. This technology is used to regenerate critical-sized bone defects in osteoporotic mice by targeting Gsk-3b to activate the osteoblastic activity of endogenous stem cells, thus addressing a critical challenge in regenerative medicine of achieving cell-free scaffold-based miRNA therapy for tissue engineering.
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