Sandwich-type PLLA-nanosheets loaded with BMP-2 induce bone regeneration in critical-sized mouse calvarial defects
Sandwich-type PLLA-nanosheets loaded with BMP-2 induce bone regeneration in critical-sized mouse calvarial defects
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DOI：
10.1016/j.actbio.2017.06.041
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发表时间：
2017-09-01
影响因子：
9.7
通讯作者：
Saito, Taku
中科院分区：
文献类型：
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作者：
Huang, Kuo-Chin;Yano, Fumiko;Saito, Taku
为了克服大面积骨缺损引起的严重临床问题，人们研究了各种骨再生方法，包括组织工程、生物材料、干细胞和药物筛选。以前，我们开发了一个独立的可生物降解的聚合物纳米片组成的聚（L-乳酸）（PLLA），使用一个简单的制造过程，包括旋涂和剥离技术。在这里，我们加载两个60 nm厚的PLLA纳米片之间的重组人骨形态发生蛋白-2（rhBMP-2），并研究这些骨再生应用中的骨形成型纳米片。PLLA纳米片在体外显示出负载rhBMP-2的恒定和持续释放超过2个月。此外，我们将含有或不含rhBMP-2的纳米片植入小鼠颅骨的临界尺寸缺损中。骨再生在植入后4周是明显的，并且在植入rhBMP-2负载的纳米片的小鼠中，再生骨的尺寸和坚固性在植入后8周增加，而在植入空白纳米片的小鼠中，在20周的时间内没有显著的骨形成。负载rhBMP-2的PLLA纳米片可能在骨再生医学中有用;此外，这种新型的PLLA纳米片结构还可以作为其他分子或药物的有效缓释载体。可生物降解的60 nm厚的PLLA纳米片显示出强粘附性，而无需任何粘合剂。在体外实验中，该纳米片可持续释放rhBMP-2超过2个月。当将含有rhBMP-2的纳米片植入小鼠颅骨的临界尺寸缺损时，它们显著增强了骨再生。除了它们用于骨再生的应用之外，PLLA纳米片可以与各种药物或分子组合用于各种目的，因为它们显示出作为缓释载体的优异能力。(C)2017 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
To overcome serious clinical problems caused by large bone defects, various approaches to bone regeneration have been researched, including tissue engineering, biomaterials, stem cells and drug screening. Previously, we developed a free-standing biodegradable polymer nanosheet composed of poly(L-lactic acid) (PLLA) using a simple fabrication process consisting of spin-coating and peeling techniques. Here, we loaded recombinant human bone morphogenetic protein-2 (rhBMP-2) between two 60-nm-thick PLLA nanosheets, and investigated these sandwich-type nanosheets in bone regeneration applications. The PLLA nanosheets displayed constant and sustained release of the loaded rhBMP-2 for over 2 months in vitro. Moreover, we implanted the sandwich-type nanosheets with or without rhBMP-2 into critical sized defects in mouse calvariae. Bone regeneration was evident 4 weeks after implantation, and the size and robustness of the regenerated bone had increased by 8 weeks after implantation in mice implanted with the rhBMP-2-loaded nanosheets, whereas no significant bone formation occurred over a period of 20 weeks in mice implanted with blank nanosheets. The PLLA nanosheets loaded with rhBMP-2 may be useful in bone regenerative medicine; furthermore, the sandwich-type PLLA nanosheet structure may potentially be applied as a potent prolonged sustained-release carrier of other molecules or drugs.Statements of SignificanceHere we describe sandwich-type poly(L-lactic acid) (PLLA) nanosheets loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) as a novel method for bone regeneration. Biodegradable 60-nm-thick PLLA nanosheets display strong adhesion without any adhesive agent. The sandwich-type PLLA nanosheets displayed constant and sustained release of the loaded rhBMP-2 for over 2 months in vitro. The nanosheets with rhBMP-2 markedly enhanced bone regeneration when they were implanted into critical-sized defects in mouse calvariae. In addition to their application for bone regeneration, PLLA nanosheets may be useful for various purposes in combination with various drugs or molecules, because they displays excellent capacity as a sustained-release carrier. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.