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

Nat Commun. 2016 Jan 14;7:10376. doi: 10.1038/ncomms10376.


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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bone Regeneration
  • Cells, Cultured
  • Female
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Guided Tissue Regeneration*
  • Mice, Inbred C57BL
  • MicroRNAs / administration & dosage*
  • Osteoporosis / therapy*
  • Polymers / chemical synthesis*
  • Tissue Scaffolds*


  • MicroRNAs
  • Mirn26 microRNA, mouse
  • Polymers
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Glycogen Synthase Kinase 3