Abstract
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.
Highlights
Autologous bone grafts are widely used in the clinical treatment of bone defects in maxillofacial and plastic surgery [1,2,3]
Bone morphogenetic protein 2 (BMP-2), a secreted growth factor that belongs to the transforming growth factor-β (TGF-β) superfamily, has attracted considerable attention because of its strong osteoinductivity [11,12]
A series of four polycarboxylates were demonstrated for enhancing the osteoinductivity of BMP-2
Summary
Autologous bone grafts are widely used in the clinical treatment of bone defects in maxillofacial and plastic surgery [1,2,3]. High doses of BMP-2 are required to maintain its activity in the long term and to regenerate a wide. It wide range range of of bone bone defects. The effect of sulfated and sulfonated polymers in modulating activity radial defect [27,28]. The effect of sulfated and sulfonated polymers in modulating thethe activity of of BMP-2 observed for other growth basic fibroblast factor. Charged negatively charged polycarboxylates offer anproperty appealing for theoffabrication of Sulfated and sulfonated polymers have been widely investigated for the modulation of growth factor biomaterials. Sulfated and sulfonated polymers have been widely investigated for the modulation of activity, but negligible have been reported onbeen polycarboxylates. 1), in enhancing the osteogenic differentiation efficiency of BMP-2
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