title: 3D-printed hierarchical scaffold for localized isoniazid/rifampin drug delivery and osteoarticular tuberculosis therapy.
abstract: 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.
authors: School of Materials Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
authors: Min
authors: M
authors: Zhu
authors: Department of Orthopedics, Changzheng Hospital of Second Military Medical University, Shanghai 200003, China.
authors: Kun
authors: K
authors: Li
authors: School of Materials Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China. Electronic address: zjf2412@163.com.
authors: Yufang
authors: Y
authors: Zhu
authors: School of Materials Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
authors: Jianhua
authors: J
authors: Zhang
authors: Department of Orthopedics, Changzheng Hospital of Second Military Medical University, Shanghai 200003, China. Electronic address: yexj2002@163.com.
authors: Xiaojian
authors: X
authors: Ye
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D005898:Glass; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D007677:Kidney Function Tests; D008099:Liver / Q000187:drug effects; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D010012:Osteogenesis / Q000187:drug effects; D016062:Porosity; D011208:Powders; D066330:Printing, Three-Dimensional; D011817:Rabbits; D011859:Radiography; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use*; D012822:Silicon Dioxide / Q000737:chemistry; D013696:Temperature; D054457:Tissue Scaffolds / Q000737:chemistry*; D014394:Tuberculosis, Osteoarticular / Q000188:drug therapy
chemical_list: D011208:Powders; D012822:Silicon Dioxide; D007538:Isoniazid; D012293:Rifampin
keywords: Localized drug release; Long-term antituberculosis therapy; Mesoporous bioceramics; Multi-drug delivery