Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects

Xiaojin Zhang, Yan Li, Y. Eugene Chen, Jihua Chen () and Peter X. Ma ()
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Xiaojin Zhang: University of Michigan
Yan Li: University of Michigan
Y. Eugene Chen: Frankel Cardiovascular Center, University of Michigan
Jihua Chen: State Key Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University
Peter X. Ma: University of Michigan

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract 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-3β 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.

Date: 2016
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DOI: 10.1038/ncomms10376

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