Experimental study of rhBMP-2 chitosan nano-sustained release carrier-loaded PLGA/nHA scaffolds to construct mandibular tissue-engineered bone

被引:55
作者
Deng, Nan [1 ,2 ]
Sun, Jian [1 ,2 ,3 ,4 ]
Li, Yali [5 ]
Chen, Liqiang [1 ]
Chen, Chen [1 ]
Wu, Yutong [1 ,2 ]
Wang, Zhihao [1 ,2 ]
Li, Li [1 ,2 ]
机构
[1] Qingdao Univ, Dept Oral & Maxillofacial Surg, Affiliated Hosp, 16 Jiangsu Rd, Qingdao 266003, Shandong, Peoples R China
[2] Qingdao Univ, Sch Stomatol, Qingdao, Shandong, Peoples R China
[3] Dent Digital Med & 3D Printing Engn Lab Qingdao, Qingdao, Shandong, Peoples R China
[4] Shandong Prov Key Lab Digital Med & Comp Assisted, Qingdao, Shandong, Peoples R China
[5] Qingdao Univ, Affiliated Hosp, Dept Operating Room, Qingdao, Shandong, Peoples R China
关键词
Drug delivery; Nanoparticle; Scaffold; Bone morphogenetic protein; Tissue regeneration; DELIVERY;
D O I
10.1016/j.archoralbio.2019.03.023
中图分类号
R78 [口腔科学];
学科分类号
100302 [口腔临床医学];
摘要
Objectives: To develop PLGA/nHA scaffold containing BMP-2 cell growth factor chitosan sustained release system as tissue engineered bone for repairing large jaw defects, test its sustained release rhBMP-2 efficiency in vitro, and evaluate its Osteogenesis in rabbit mandibular defects. Methods: Tissue engineered bone scaffold complexes were prepared by complexing rhBMP-2 loaded chitosan (CS / rhBMP-2) nano sustained release carrier with PLGA / nHA scaffold carrier by 3D printing. In vitro, the porosity, pore size and degradation rate and the dose-time effect relationship of cytokine release were examined. Micro-CT, hematoxylin/eosin staining, Masson staining and immunohistochemistry were determined at week 4, week 8 and week 12 in 18 rabbits. Results: In vitro, the porosity was (73.64 +/- 1.82)%, and the average pore diameter was (431.31 +/- 18.40) mu m. The cumulative release was only 9.54 +/- 0.86% within 48 h and 61.38 +/- 2.39% on the 30th day. In vivo, Micro-CT examination showed that the BMD and the bone volume fraction at 4, 8, and 12 weeks were higher in the implantation group than in the control group. In the 12th week, Masson staining showed that new bone occupied 19.2% of the defect area in the control group, whereas the proportion of new bone reached 45.5% in the experimental group. Conclusions: PLGA/nHA/CS/rhBMP-2 scaffold complex effectively controlled the early burst effect of rhBMP-2. The bone tissue engineering scaffold complex had good biocompatibility and induced osteogenic effects. It successfully repaired the experimental bone defect area of the rabbit mandible.
引用
收藏
页码:16 / 25
页数:10
相关论文
共 31 条
[1]
Complications of Recombinant Human BMP-2 for Treating Complex Tibial Plateau Fractures: A Preliminary Report [J].
Boraiah, Sreevathsa ;
Paul, Omesh ;
Hawkes, David ;
Wickham, Matthew ;
Lorich, Dean G. .
CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, 2009, 467 (12) :3257-3262
[2]
In situ handheld three-dimensional bioprinting for cartilage regeneration [J].
Di Bella, Claudia ;
Duchi, Serena ;
O'Connell, Cathal D. ;
Blanchard, Romane ;
Augustine, Cheryl ;
Yue, Zhilian ;
Thompson, Fletcher ;
Richards, Christopher ;
Beirne, Stephen ;
Onofrillo, Carmine ;
Bauquier, Sebastien H. ;
Ryan, Stewart D. ;
Pivonka, Peter ;
Wallace, Gordon G. ;
Choong, Peter F. .
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, 2018, 12 (03) :611-621
[3]
The Influence of Copolymer Composition on PLGA/nHA Scaffolds' Cytotoxicity and In Vitro Degradation [J].
Diaz, Esperanza ;
Puerto, Igor ;
Ribeiro, Silvie ;
Lanceros-Mendez, Senentxu ;
Manuel Barandiarian, Jose .
NANOMATERIALS, 2017, 7 (07)
[4]
Functional block of IL-17 cytokine promotes bone healing by augmenting FOXO1 and ATF4 activity in cortical bone defect model [J].
Dixit, M. ;
Singh, K. B. ;
Prakash, R. ;
Singh, D. .
OSTEOPOROSIS INTERNATIONAL, 2017, 28 (07) :2207-2220
[5]
Insulin Signaling in Osteoblasts Integrates Bone Remodeling and Energy Metabolism [J].
Ferron, Mathieu ;
Wei, Jianwen ;
Yoshizawa, Tatsuya ;
Del Fattore, Andrea ;
DePinho, Ronald A. ;
Teti, Anna ;
Ducy, Patricia ;
Karsenty, Gerard .
CELL, 2010, 142 (02) :296-308
[6]
Nanomaterials and bone regeneration [J].
Gong, Tao ;
Xie, Jing ;
Liao, Jinfeng ;
Zhang, Tao ;
Lin, Shiyu ;
Lin, Yunfeng .
BONE RESEARCH, 2015, 3
[7]
PLGA/nHA hybrid nanofiber scaffold as a nanocargo carrier of insulin for accelerating bone tissue regeneration [J].
Haider, Adnan ;
Gupta, Kailash Chandra ;
Kang, Inn-Kyu .
NANOSCALE RESEARCH LETTERS, 2014, 9 :1-12
[8]
Long-term delivery enhances in vivo osteogenic efficacy of bone morphogenetic protein-2 compared to short-term delivery [J].
Jeon, Oju ;
Song, Su Jin ;
Yang, Hee Seok ;
Bhang, Suk-Ho ;
Kang, Sun-Woong ;
Sung, Mi Ae ;
Lee, Jong Ho ;
Kim, Byung-Soo .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 369 (02) :774-780
[9]
3D printing in pharmaceutics: A new tool for designing customized drug delivery systems [J].
Jonathan, Goole ;
Karim, Amighi .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2016, 499 (1-2) :376-394
[10]
Guided self-organization and cortical plate formation in human brain organoids [J].
Lancaster, Madeline A. ;
Corsini, Nina S. ;
Wolfinger, Simone ;
Gustafson, E. Hilary ;
Phillips, Alex W. ;
Burkard, Thomas R. ;
Otani, Tomoki ;
Livesey, Frederick J. ;
Knoblich, Juergen A. .
NATURE BIOTECHNOLOGY, 2017, 35 (07) :659-+