Journal
POLYMERS
Volume 11, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/polym11081327
Keywords
bone morphogenetic protein-2; osteogenic differentiation; polyelectrolyte complex; polycarboxylate; poly(glutamic acid)
Categories
Funding
- Sasakawa Scientific Research Grant from the Japan Science Society
- TMDU President's Young Researchers Award
- Japan Society for the Promotion of Science (JSPS) (JSPS KAKENHI) [JP19K19224]
- JSPS (JSPS KAKENHI) [JP18K19904, JP17K11901, JP16H01852]
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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.
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