Light-triggered RNA release and induction of hMSC osteogenesis via photodegradable, dual-crosslinked hydrogels

Nanomedicine (Lond). 2016 Jun;11(12):1535-50. doi: 10.2217/nnm-2016-0088. Epub 2016 Jun 1.

Abstract

Aim: To engineer a photodegradable hydrogel system for actively controlled release of bioactive unmodified RNA at designated time points to induce hMSC osteogenesis.

Materials & methods: RNA/polyethylenimine complexes were loaded into dual-crosslinked photodegradable hydrogels to examine the capacity of UV light application to trigger their release. The ability of released RNA to drive hMSC osteogenic differentiation was also investigated.

Results & conclusion: RNA release from photodegradable hydrogels was accelerated upon UV application, which was not observed in non-photodegradable hydrogels. Regardless of the presence of UV light, released siGFP exhibited high bioactivity by silencing GFP expression in HeLa cells. Importantly, siNoggin or miRNA-20a released from the hydrogels induced hMSC osteogenesis. This system provides a potentially valuable physician/patient-controlled 'on-demand' RNA delivery platform for biomedical applications.

Keywords: UV-controllable release; bone tissue engineering; in situ forming hydrogel; miRNA; on-demand release; photolabile hydrogels; siRNA; stem cell differentiation.

MeSH terms

  • Cell Differentiation
  • Cell Line
  • Delayed-Action Preparations / chemistry*
  • HeLa Cells
  • Humans
  • Hydrogels / chemistry*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • MicroRNAs / administration & dosage*
  • MicroRNAs / genetics
  • Osteogenesis*
  • Photolysis*
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics
  • Tissue Engineering
  • Ultraviolet Rays

Substances

  • Delayed-Action Preparations
  • Hydrogels
  • MIRN20a microRNA, human
  • MicroRNAs
  • RNA, Small Interfering