Terauchi Masahiko, Ikeda Go, Nishida Kei, Tamura Atsushi, Yamaguchi Satoshi, Harada Kiyoshi, Yui Nobuhiko
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.
Macromol Biosci. 2015 Jul;15(7):953-64. doi: 10.1002/mabi.201500032. Epub 2015 Mar 23.
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.
尽管骨形态发生蛋白-2（BMP-2）因其强大的骨诱导活性而备受关注，但其在生理条件下会发生降解和失活，这限制了其临床应用。已知带负电荷的肝素可与BMP-2形成聚电解质复合物，以防止其失活并增强BMP-2的骨诱导能力。在此，我们报道了由α-环糊精缠绕在线性聚合物上组成的磺化聚轮烷（S-PRX），它可通过形成聚电解质复合物来保护BMP-2。当用S-PRX/BMP-2复合物处理MC3T3-E1骨祖细胞时，与游离BMP-2和肝素/BMP-2复合物相比，观察到显著更高的碱性磷酸酶产生和矿化基质沉积。需要注意的是，S-PRX显示出可忽略不计的抗凝活性和细胞毒性，而肝素显示出较强的抗凝活性。因此，S-PRX有望成为增强BMP-2骨诱导能力且无毒性和抗凝活性的候选物，并可为临床骨再生做出贡献。
