Enhanced loading and controlled release of rhBMP-2 in thin mineralized collagen coatings with the aid of chitosan nanospheres and its biological evaluations
Enhanced loading and controlled release of rhBMP-2 in thin mineralized collagen coatings with the aid of chitosan nanospheres and its biological evaluations
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借助壳聚糖纳米球增强矿化胶原蛋白薄层中 rhBMP-2 的负载和控制释放及其生物学评价
DOI：
10.1039/c4tb00404c
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发表时间：
2014-01-01
影响因子：
7
通讯作者：
Wang, Huiming
中科院分区：
文献类型：
--
作者：
Kong, Ziqiang;Lin, Jun;Wang, Huiming
负载适量的rhBMP-2并避免其“突释”是提高金属植入物薄生物活性涂层生物学性能的关键挑战。本研究利用壳聚糖对蛋白质的良好亲和性和纳米球的大比表面积，采用壳聚糖纳米球与矿化胶原涂层复合的方法，提高rhBMP-2的载药量，改善rhBMP-2的释放行为。我们采用电泳进样的方法实现了掺入过程。使用壳聚糖纳米球，我们能够将薄涂层中的rhBMP-2负载量增加2.7倍（从446 ng cm（-2）增加到1186 ng cm（-2）），并表明rhBMP-2表现出持续释放行为。MC 3 T3-E1细胞在rhBMP-2/壳聚糖纳米微球复合薄涂层（Col/Cs/BMP）上培养，显示出良好的细胞粘附和增殖行为，以及高水平的分化和矿化。在体实验中，螺旋CT分析和组织学观察表明，Col/Cs/BMP涂层在金属种植体上植入4 ~ 8周后能增加骨密度，促进新骨生长，植入8周后宿主骨与新骨的边界消失。拔出试验进一步证实了Col/Cs/BMP涂层可以显著增强骨整合。结果表明，壳聚糖纳米微球的加入可以适当提高骨载体的载药量，改善rhBMP-2的释放行为，促进骨结合。
Loading of an appropriate amount of rhBMP-2 and avoiding its "burst-release" are key challenges for upgrading the biological performance of thin bioactive coatings on metal implants. In this study, we adopted incorporation of chitosan nanospheres into thin mineralized collagen coatings to enhance rhBMP-2 loading and improve releasing behavior based on the good affinity of chitosan for proteins and the large surface area of nanospheres. We realized the incorporation process by electrophoretic injection. Using chitosan nanospheres, we were able to increase the rhBMP-2 loading amount in the thin coating by 2.7-fold (from 446 ng cm(-2) to 1186 ng cm(-2)), and showed that the rhBMP-2 exhibited sustained release behavior. MC3T3-E1 cells cultured on the rhBMP-2/chitosan nanosphere-incorporated thin coatings (Col/Cs/BMP) showed good cell attachment and proliferative behavior, and high levels of differentiation and mineralization. In in vivo tests, spiral CT analysis and histological observations demonstrated that Col/Cs/BMP coatings on metal implants were able to increase bone density and accelerate new bone growth after implantation for 4 to 8 weeks, and the boundary between host bones and new bones disappeared after implantation for 8 weeks. The pull-out tests further confirmed that the Col/Cs/BMP coatings could significantly enhance osseointegration. The present results indicate that incorporation of chitosan nanospheres into thin coatings is an effective way to enhance the loading amount properly, improve the release behavior of rhBMP-2 and finally accelerate the osseointegration process.