期刊
ACTA BIOMATERIALIA
卷 16, 期 -, 页码 145-155出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2015.01.034
关键词
Mesoporous bioceramics; Multi-drug delivery; Localized drug release; Long-term antituberculosis therapy
资金
- National Nature Science Foundation of China [51302170]
- Shanghai Nature Science Foundation [13ZR1458600]
- Innovation Program of Shanghai Municipal Education Commission [14YZ085]
- National High Technology Research and Development Program of the Science and Technology (863 Program) [2013AA032203]
- Shanghai Nanometer Special Project [11nm0504200]
After surgical treatment of osteoarticular tuberculosis (TB), it is necessary to fill the surgical defect with an implant, which combines the merits of osseous regeneration and local multi-drug therapy so as to avoid drug resistance and side effects. In this study, a 3D-printed macro/meso-porous composite scaffold is fabricated. High dosages of isoniazid (INH)/rifampin (RFP) anti-TB drugs are loaded into chemically modified mesoporous bioactive ceramics in advance, which are then bound with poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) through a 3D printing procedure. The composite scaffolds show greatly prolonged drug release time compared to commercial calcium phosphate scaffolds either in vitro or in vivo. In addition, the drug concentrations on the periphery tissues of defect are maintained above INH/RFP minimal inhibitory concentrations even up to 12 weeks post-surgery, while they are extremely low in blood. Examinations of certain serum enzymes suggest no harm to hepatic or renal functions. Micro-CT evaluations and histology results also indicate partly degradation of the composite scaffolds and new bone growth in the cavity. These results suggest promising applications of our hierarchical composite scaffold in bone regeneration and local anti-TB therapy after osteoarticular TB debridement surgery. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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