Scaffold-mediated BMP-2 minicircle DNA delivery accelerated bone repair in a mouse critical-size calvarial defect model

J Biomed Mater Res A. 2016 Aug;104(8):2099-107. doi: 10.1002/jbm.a.35735. Epub 2016 Jun 3.

Abstract

Scaffold-mediated gene delivery holds great promise for tissue regeneration. However, previous attempts to induce bone regeneration using scaffold-mediated non-viral gene delivery rarely resulted in satisfactory healing. We report a novel platform with sustained release of minicircle DNA (MC) from PLGA scaffolds to accelerate bone repair. MC was encapsulated inside PLGA scaffolds using supercritical CO2 , which showed prolonged release of MC. Skull-derived osteoblasts transfected with BMP-2 MC in vitro result in higher osteocalcin gene expression and mineralized bone formation. When implanted in a critical-size mouse calvarial defect, scaffolds containing luciferase MC lead to robust in situ protein production up to at least 60 days. Scaffold-mediated BMP-2 MC delivery leads to substantially accelerated bone repair as early as two weeks, which continues to progress over 12 weeks. This platform represents an efficient, long-term nonviral gene delivery system, and may be applicable for enhancing repair of a broad range of tissues types. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2099-2107, 2016.

Keywords: BMP2; bone regeneration; minicircle; scaffold.

Publication types

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

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / administration & dosage*
  • Bone Morphogenetic Protein 2 / metabolism
  • DNA, Circular / metabolism*
  • Gene Transfer Techniques*
  • Luciferases / metabolism
  • Mice
  • Mice, Nude
  • Osteogenesis
  • Polyglycolic Acid / chemistry
  • Skull / pathology*
  • Tissue Scaffolds / chemistry*
  • Up-Regulation
  • Wound Healing*
  • X-Ray Microtomography

Substances

  • Bone Morphogenetic Protein 2
  • DNA, Circular
  • Polyglycolic Acid
  • Luciferases