Huang Kuo-Chin, Yano Fumiko, Murahashi Yasutaka, Takano Shuta, Kitaura Yoshiaki, Chang Song Ho, Soma Kazuhito, Ueng Steve W N, Tanaka Sakae, Ishihara Kazuhiko, Okamura Yosuke, Moro Toru, Saito Taku
Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33302, Taiwan.
Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; Bone and Cartilage Regenerative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Acta Biomater. 2017 Sep 1;59:12-20. doi: 10.1016/j.actbio.2017.06.041. Epub 2017 Jun 27.
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 2months 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 4weeks after implantation, and the size and robustness of the regenerated bone had increased by 8weeks after implantation in mice implanted with the rhBMP-2-loaded nanosheets, whereas no significant bone formation occurred over a period of 20weeks 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.
Here 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 2months 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.
为克服大骨缺损引起的严重临床问题，人们研究了多种骨再生方法，包括组织工程、生物材料、干细胞和药物筛选。此前，我们使用由旋涂和剥离技术组成的简单制造工艺，开发了一种由聚（L-乳酸）（PLLA）组成的独立式可生物降解聚合物纳米片。在此，我们将重组人骨形态发生蛋白-2（rhBMP-2）负载在两个60纳米厚的PLLA纳米片之间，并研究了这些三明治型纳米片在骨再生应用中的情况。PLLA纳米片在体外2个多月内显示出负载的rhBMP-2持续稳定释放。此外，我们将含或不含rhBMP-2的三明治型纳米片植入小鼠颅骨的临界尺寸缺损处。植入后4周骨再生明显，在植入负载rhBMP-2纳米片的小鼠中，植入后8周再生骨的大小和坚固性增加，而植入空白纳米片的小鼠在20周内未发生明显骨形成。负载rhBMP-2的PLLA纳米片可能在骨再生医学中有用；此外，三明治型PLLA纳米片结构可能潜在地用作其他分子或药物的有效长效缓释载体。
在此，我们描述了负载重组人骨形态发生蛋白-2（rhBMP-2）的三明治型聚（L-乳酸）（PLLA）纳米片作为一种骨再生的新方法。可生物降解的60纳米厚PLLA纳米片在无任何粘合剂的情况下显示出强粘附性。三明治型PLLA纳米片在体外2个多月内显示出负载的rhBMP-2持续稳定释放。当将含rhBMP-2的纳米片植入小鼠颅骨的临界尺寸缺损处时，显著增强了骨再生。除了用于骨再生外，PLLA纳米片作为缓释载体具有优异的能力，可能与各种药物或分子结合用于各种目的。
