Journal
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
Volume 105, Issue 5, Pages 1355-1363Publisher
WILEY
DOI: 10.1002/jbm.a.36016
Keywords
bone morphogenetic protein-2; bone regeneration; polyrotaxane; cyclodextrin; polyelectrolyte complex
Funding
- Grants-in-Aid for Scientific Research [17K11901, 16H01852] Funding Source: KAKEN
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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 alpha-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. (C) 2017 Wiley Periodicals, Inc.
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