Effective Immobilization of BMP-2 Mediated by Polydopamine Coating on Biodegradable Nanofibers for Enhanced in Vivo Bone Formation

被引:181
作者
Cho, Hyeong-jin [1 ]
Perikamana, Sajeesh Kumar Madhurakkat [1 ]
Lee, Ji-hye [1 ]
Lee, Jinkyu [1 ]
Lee, Kyung-Mi [2 ]
Shin, Choongsoo S. [3 ]
Shin, Heungsoo [1 ]
机构
[1] Hanyang Univ, Inst Bioengn & Biopharmaceut Res, Dept Bioengn, Seoul 133791, South Korea
[2] Korea Univ, Dept Biochem & Mol Biol, Global Res Lab, Coll Med, Seoul 136713, South Korea
[3] Sogang Univ, Dept Mech Engn, Seoul 121742, South Korea
基金
新加坡国家研究基金会;
关键词
guided bone regeneration; bone morphogenic proteins; nanofibers; electrospinning; osteogenic differentiation; polydopamine; MESENCHYMAL STEM-CELLS; TISSUE ENGINEERING APPLICATIONS; MORPHOGENETIC PROTEIN-2; OSTEOGENIC DIFFERENTIATION; SURFACE FUNCTIONALIZATION; ELECTROSPUN FIBERS; GROWTH-FACTORS; REGENERATION; TITANIUM; SCAFFOLDS;
D O I
10.1021/am501391z
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Although bone morphogenic proteins (BMPs) have been widely used for bone regeneration, the ideal delivery system with optimized dose and minimized side effects is still active area of research. In this study, we developed bone morphogenetic protein-2(BMP-2) immobilized poly(L-lactide) (PLLA) nanofibers inspired by polydopamine, which could be ultimately used as membranes for guided bone regeneration, and investigated their effect on guidance of in vitro cell behavior and in vivo bone formation. Surface chemical analysis of the nanofibers confirmed successful immobilization of BMP-2 mediated by polydopamine, and about 9096 of BMP-2 was stably retained on the nanofiber surface for at least 28 days. The alkaline phosphatase activity and calcium mineralization of human mesenchymal stem cells (hMSCs) after 14 days of in vitro culture was significantly enhanced on nanofibers immobilized with BMP-2. More importantly, BMP-2 at a relatively small dose was highly active following implantation to the critical-sized defect in the cranium of mice; radiographic analysis demonstrated that 77.8 +/- 11.796 of newly formed bone was filled within the defect for a BMP-2-immobilized groups at the concentration of 124 +/- 9 ng/cm(2), as compared to 5.9 +/- 1.0 and 34.1 +/- 5.5% recovery, for a defect-only and a polydopamine-only group, respectively. Scanning and transmission electron microscopy of samples from the BMP-2 immobilized group showed fibroblasts and osteoblasts with nanofiber strands in the middle of regenerated bone tissue, revealing the importance of interaction between implanted nanofibers and the neighboring extracellular environment. Taken together, our data support that the presentation of BMP-2 on the surface of nanofibers as immobilized by utilizing polydopamine chemistry may be an effective method to direct bone growth at relatively low local concentration.
引用
收藏
页码:11225 / 11235
页数:11
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