Potentiating bioactivity of BMP-2 by polyelectrolyte complexation with sulfonated polyrotaxanes to induce rapid bone regeneration in a mouse calvarial defect

J Biomed Mater Res A. 2017 May;105(5):1355-1363. doi: 10.1002/jbm.a.36016. Epub 2017 Feb 24.

Abstract

Bone reconstruction is a challenging issue in the regeneration of surgically removed bone and disease-related bone defects. Although bone morphogenetic protein-2 (BMP-2) has received considerable attention as a bone regeneration inducer, a high dose of BMP-2 is typically required due to its short life-time under in vivo conditions. We have proposed a method to enhance the osteogenetic differentiation ability of BMP-2 in vitro that is based on supramolecular polyelectrolyte complexation with sulfonated polyrotaxanes (PRXs) consisting of sulfopropyl ether (SPE)-modified α-cyclodextrins threaded along a poly(ethylene glycol) chain capped with terminal bulky stopper molecules. In this study, we evaluated the in vivo bone regeneration ability of the SPE-PRX/BMP-2 complexes in a mouse calvarial defect model in comparison to free BMP-2 and heparin/BMP-2 complexes. The regenerated bone area was determined by X-ray computed microtomography, and the mice implanted with sulfonated PRX/BMP-2 complexes exhibited rapid and significant bone regeneration compared to those implanted with free BMP-2 and heparin/BMP-2 complexes. We concluded that the sulfonated PRX/BMP-2 complexes are a promising candidate for clinical bone regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1355-1363, 2017.

Keywords: bone morphogenetic protein-2; bone regeneration; cyclodextrin; polyelectrolyte complex; polyrotaxane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2* / chemistry
  • Bone Morphogenetic Protein 2* / pharmacokinetics
  • Bone Morphogenetic Protein 2* / pharmacology
  • Bone Regeneration / drug effects*
  • Cell Line
  • Mice
  • Osteoblasts / metabolism*
  • Osteoblasts / pathology
  • Polyelectrolytes* / chemistry
  • Polyelectrolytes* / pharmacology
  • Rotaxanes* / chemistry
  • Rotaxanes* / pharmacology
  • Skull / injuries*
  • Skull / metabolism*
  • Skull / pathology

Substances

  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Polyelectrolytes
  • Rotaxanes