Supramolecular Polyelectrolyte Complexes of Bone Morphogenetic Protein-2 with Sulfonated Polyrotaxanes to Induce Enhanced Osteogenic Differentiation.

Masahiko Terauchi, Go Ikeda, Kei Nishida, Atsushi Tamura, Satoshi Yamaguchi, Kiyoshi Harada, Nobuhiko Yui

Index: Macromol. Biosci. 15 , 953-64, (2015)

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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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.