title: Supramolecular Polyelectrolyte Complexes of Bone Morphogenetic Protein-2 with Sulfonated Polyrotaxanes to Induce Enhanced Osteogenic Differentiation.
abstract: Although bone morphogenetic protein-2 (BMP-2) has received considerable attention because of its strong osteoinductivity, the clinical application of BMP-2 is limited due to its degradation and deactivation under physiological conditions. Negatively charged heparin is known to form polyelectrolyte complexes with BMP-2 to prevent deactivation and enhance the osteoinduction capability of BMP-2. Herein, we report the sulfonated polyrotaxanes (S-PRX) composed of α-cyclodextrin threaded onto a linear polymer for the protection of BMP-2 through the polyelectrolyte complex formation. When MC3T3-E1 osteoprogenitor cells were treated with the S-PRX/BMP-2 complexes, significantly high alkaline phosphatase production and mineralized matrix deposition were observed compared with that of free BMP-2 and heparin/BMP-2 complexes. Note that the S-PRXs showed negligible anticoagulant activity and cytotoxicity, whereas heparin showed strong anticoagulant activity. Accordingly, the S-PRXs are promising candidates for enhanced osteoinduction ability of BMP-2 without toxicity and anticoagulant activity and could contribute to clinical bone regeneration.
authors: 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.|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: Masahiko
authors: M
authors: Terauchi
authors: 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: Go
authors: G
authors: Ikeda
authors: 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: Kei
authors: K
authors: Nishida
authors: 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: Atsushi
authors: A
authors: Tamura
authors: 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: Satoshi
authors: S
authors: Yamaguchi
authors: 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. haradak.mfs@tmd.ac.jp.
authors: Kiyoshi
authors: K
authors: Harada
authors: Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo, 101-0062, Japan. yui.org@tmd.ac.jp.
authors: Nobuhiko
authors: N
authors: Yui
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry* / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects*; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects*; D043862:Rotaxanes / Q000737:chemistry* / Q000494:pharmacology; D047391:alpha-Cyclodextrins
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D043862:Rotaxanes; D047391:alpha-Cyclodextrins; C032613:alpha-cyclodextrin
keywords: BMP-2; blood coagulation; bone regeneration; heparin; polyrotaxane