title: Potentiating bioactivity of BMP-2 by polyelectrolyte complexation with sulfonated polyrotaxanes to induce rapid bone regeneration in a mouse calvarial defect.
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.
authors.affiliation: Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8549, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Terauchi
authors.affiliation: Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8549, Japan.
authors.forename: Takasuke
authors.initials: T
authors.lastname: Inada
authors.affiliation: Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8549, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kanemaru
authors.affiliation: Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo, 101-0062, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Ikeda
authors.affiliation: Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo, 101-0062, Japan.
authors.forename: Asato
authors.initials: A
authors.lastname: Tonegawa
authors.affiliation: Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo, 101-0062, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Nishida
authors.affiliation: Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo, 101-0062, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Arisaka
authors.affiliation: Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo, 101-0062, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tamura
authors.affiliation: Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8549, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo, 101-0062, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Yui
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects*; D002460:Cell Line; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D000071228:Polyelectrolytes / Q000737:chemistry / Q000494:pharmacology; D043862:Rotaxanes / Q000737:chemistry / Q000494:pharmacology; D012886:Skull / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D000071228:Polyelectrolytes; D043862:Rotaxanes
keywords: bone morphogenetic protein-2; bone regeneration; cyclodextrin; polyelectrolyte complex; polyrotaxane