Terauchi Masahiko, Tamura Atsushi, Tonegawa Asato, Yamaguchi Satoshi, Yoda Tetsuya, Yui Nobuhiko
Department of Maxillofacial Surgery, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo, Tokyo 113-8549, Japan.
Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan.
Polymers (Basel). 2019 Aug 9;11(8):1327. doi: 10.3390/polym11081327.
Bone morphogenetic protein 2 (BMP-2) has received considerable attention because of its osteoinductivity, but its use is limited owing to its instability and adverse effects. To reduce the dose of BMP-2, complexation with heparin is a promising approach, because heparin enhances the osteoinductivity of BMP-2. However, the clinical use of heparin is restricted because of its anticoagulant activity. Herein, to explore alternative polymers that show heparin-like activity, four polycarboxylates, poly(acrylic acid) (PAA), poly(methacrylic acid) (PMAA), poly(aspartic acid) (PAsp), and poly(glutamic acid) (PGlu), were selected and their capability to modulate the osteoinductivity of BMP-2 was evaluated. Dynamic light scattering indicated that these polycarboxylates formed polyelectrolyte complexes with BMP-2. The osteogenic differentiation efficiency of MC3T3-E1 cells treated with the polycarboxylate/BMP-2 complexes was investigated in comparison to that of the heparin/BMP-2 complex. As a result, PGlu/BMP-2 complex showed the highest activity of alkaline phosphatase, which is an early-stage marker of osteogenic differentiation, and rapid mineralization. Based on these observations, PGlu could serve as an alternative to heparin in the regenerative therapy of bone using BMP-2.
骨形态发生蛋白2（BMP-2）因其骨诱导活性而受到广泛关注，但其应用因稳定性和不良反应而受到限制。为了降低BMP-2的剂量，与肝素复合是一种很有前景的方法，因为肝素可增强BMP-2的骨诱导活性。然而，肝素的临床应用因其抗凝活性而受到限制。在此，为了探索具有类肝素活性的替代聚合物，选择了四种聚羧酸盐，即聚丙烯酸（PAA）、聚甲基丙烯酸（PMAA）、聚天冬氨酸（PAsp）和聚谷氨酸（PGlu），并评估了它们调节BMP-2骨诱导活性的能力。动态光散射表明，这些聚羧酸盐与BMP-2形成了聚电解质复合物。与肝素/BMP-2复合物相比，研究了用聚羧酸盐/BMP-2复合物处理的MC3T3-E1细胞的成骨分化效率。结果，PGlu/BMP-2复合物显示出最高的碱性磷酸酶活性，碱性磷酸酶是成骨分化的早期标志物，且矿化迅速。基于这些观察结果，在使用BMP-2的骨再生治疗中，PGlu可作为肝素的替代品。
