文献类型：期刊文献

英文题名：Self-assembly of dual drug-delivery coating for synergistic bone regeneration

作者：Qu, Xue[1,2];He, Fan[1,2];Tan, Haoqi[1,2];Yu, Yuanman[1,2];Axrap, Akbar[1,2,3];Wang, Meng[1,2];Dai, Kai[1,2];Zhang, Zheng[4,5];Yang, Fei[6];Wang, Shenguo[6];Kohn, Joachim[4,5];Liu, Changsheng[1,2]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Key Lab Ultrafine Mat, Minist Educ, Shanghai 200237, Peoples R China;[3]Xinjiang Med Univ, Affiliated Hosp 1, Urumqi 830054, Peoples R China;[4]Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA;[5]Rutgers State Univ, New Jersey Ctr Biomat, Piscataway, NJ 08854 USA;[6]Chinese Acad Sci, Inst Chem, State Key Lab Polymer Phys & Chem, Beijing 100190, Peoples R China

年份：2016

卷号：4

期号：28

起止页码：4901

外文期刊名：JOURNAL OF MATERIALS CHEMISTRY B

收录：;EI(收录号：20163002637618);WOS:【SCI-EXPANDED(收录号:WOS:000379570000013)】；

基金：We acknowledge support from the National Basic Research Program of China (2012CB933600), Innovation Program of Shanghai Municipal Education Commission (14ZZ060), Shanghai Science and Technology Development Funds (14QA1401000), the National Natural Science Foundation of China (51573047) and the 111 project (B14018).

语种：英文

外文关键词：Composite coatings - Targeted drug delivery - Controlled drug delivery - Self assembly - Nanoparticles - Recombinant proteins - Cytology - Bone

摘要：Bone regeneration for the treatment of bone diseases represents a major clinical need. Introducing recombinant human bone morphogenetic protein-2 (rhBMP-2) into biomaterials is an extensively used approach to induce osteogenic differentiation and accelerate bone regeneration. However, serious adverse events can occur in the event of an overdose of rhBMP-2. Dexamethasone (DEX) is a synthetic hydrophobic glucocorticoid, which can enhance rhBMP-2-induced osteogenic differentiation by binding to a glucocorticoid receptor intracellularly. In this study, we have developed a multilayered composite coating made of poly(L-lactide-co-glycolide) (PLGA) nanoparticles, heparin and chitosan to deliver DEX and rhBMP-2 dually. The coating can reserve DEX and rhBMP-2 using the building blocks of the PLGA nanoparticles and heparin. Sustained release of DEX and rhBMP-2 by this coating was achieved. Moreover, a flow cytometry assay suggests that the PLGA nanoparticles could be transported across the cell membrane and presumably could improve the intracellular delivery of DEX via cell internalization. The in vitro osteogenesis studies reveal that the dual drug-loaded coating has a synergistic osteogenic differentiation effect on C2C12 myoblasts, as indicated by the upregulation of the alkaline phosphatise activity and osteo-related gene expression. In addition, mu CT and histological analysis of the in vivo experiments demonstrate that the dual drug-loaded coating induced more ectopic bone formation than the individual drug-loaded coating. Therefore, this study demonstrates that our coating system can reserve these two drugs and deliver them locally to cells with the ability to induce rapid osteogenic differentiation and bone regeneration synergistically. Compared to other reported DEX/rhBMP-2 delivery systems, our coating system represents a simple, safe and effective dual drug delivery alternative. Moreover, since a layer-by-layer strategy is easily applied onto varying substrates, our coating system can be combined with many commercially available or existing biomaterials to improve their osteogenetic performance.