A programmed release multi-drug implant fabricated by three-dimensional printing technology for bone tuberculosis therapy

In the world, bone tuberculosis is still very difficult to treat and presents a challenge to clinicians. In this study, we utilized 3D printing technology to fabricate a programmed release multi-drug implant for bone tuberculosis therapy. The construction of the drug implant was a multi-layered concentric cylinder divided into four layers from the center to the periphery. Isoniazid and rifampicin were distributed individually into the different layers in a specific sequence of isoniazid–rifampicin–isoniazid–rifampicin. The drug release assays in vitro and in vivo showed that isoniazid and rifampicin were released orderly from the outside to the center to form the multi-drug therapeutic alliance, and the peak concentrations of drugs were detected in sequence at 8 to 12 day intervals. In addition, no negative effect on the proliferation of rabbit bone marrow mesenchymal stem cells was detected during the cytocompatibility assay. Due to its ideal pharmacologic action and cytocompatibility, the programmed release multi-drug implant with a complex construction fabricated by 3D printing technology could be of interest in prevention and treatment of bone tuberculosis.

[1]  Qixin Zheng,et al.  The controlled-releasing drug implant based on the three dimensional printing technology: Fabrication and properties of drug releasing in vivo , 2009 .

[2]  Huibi Xu,et al.  Levofloxacin implants with predefined microstructure fabricated by three-dimensional printing technique. , 2007, International journal of pharmaceutics.

[3]  M. Hussain,et al.  Continuing differentiation of human mesenchymal stem cells and induced chondrogenic and osteogenic lineages in electrospun PLGA nanofiber scaffold. , 2007, Biomaterials.

[4]  Vojo Deretic,et al.  Mechanisms of action of isoniazid , 2006, Molecular microbiology.

[5]  G. Yuan,et al.  Double glow plasma hydrogen-free carburizing on commercial purity titanium , 2005 .

[6]  Richard Tuli,et al.  Multilineage differentiation of human mesenchymal stem cells in a three-dimensional nanofibrous scaffold. , 2005, Biomaterials.

[7]  G. Gosheger,et al.  Effectiveness of hydroxyapatite-vancomycin bone cement in the treatment of Staphylococcus aureus induced chronic osteomyelitis. , 2005, Biomaterials.

[8]  A. Hanssen Local antibiotic delivery vehicles in the treatment of musculoskeletal infection. , 2005, Clinical orthopaedics and related research.

[9]  H. Seitz,et al.  Three-dimensional printing of porous ceramic scaffolds for bone tissue engineering. , 2005, Journal of biomedical materials research. Part B, Applied biomaterials.

[10]  Guo,et al.  Design and Fabrication of Drug Delivery Devices with Complex Architectures Based on Three-dimensional Printing Technique , 2005 .

[11]  V. Mendel,et al.  Therapy with gentamicin-PMMA beads, gentamicin-collagen sponge, and cefazolin for experimental osteomyelitis due to Staphylococcus aureus in rats , 2005, Archives of Orthopaedic and Trauma Surgery.

[12]  Shaochen Chen,et al.  Micro and nano-fabrication of biodegradable polymers for drug delivery. , 2004, Advanced drug delivery reviews.

[13]  F. Barry,et al.  Mesenchymal stem cells: clinical applications and biological characterization. , 2004, The international journal of biochemistry & cell biology.

[14]  Shih-Jung Liu,et al.  The release of cefazolin and gentamicin from biodegradable PLA/PGA beads. , 2004, International journal of pharmaceutics.

[15]  Julian R. Jones,et al.  Large-Scale Production of 3D Bioactive Glass Macroporous Scaffolds for Tissue Engineering , 2004 .

[16]  Qiong Wu,et al.  Attachment, proliferation and differentiation of osteoblasts on random biopolyester poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds. , 2004, Biomaterials.

[17]  A Delgado,et al.  Ciprofloxacin implants for bone infection. In vitro-in vivo characterization. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[18]  W. Friess,et al.  Collagen as a carrier for on-site delivery of antibacterial drugs. , 2003, Advanced drug delivery reviews.

[19]  Gloria R. Gogola,et al.  Antibiotic Microspheres: Preliminary Testing for Potential Treatment of Osteomyelitis , 2003, Clinical orthopaedics and related research.

[20]  K. Leong,et al.  Solid freeform fabrication of three-dimensional scaffolds for engineering replacement tissues and organs. , 2003, Biomaterials.

[21]  A. Malaviya,et al.  Arthritis associated with tuberculosis. , 2003, Best practice & research. Clinical rheumatology.

[22]  B Derby,et al.  Novel collagen scaffolds with predefined internal morphology made by solid freeform fabrication. , 2003, Biomaterials.

[23]  T. Desai,et al.  Microfabricated drug delivery systems: from particles to pores. , 2003, Advanced drug delivery reviews.

[24]  Scott C. Brown,et al.  A three-dimensional osteochondral composite scaffold for articular cartilage repair. , 2002, Biomaterials.

[25]  J. Calhoun,et al.  The application of bioimplants in the management of chronic osteomyelitis. , 2002, Orthopedics.

[26]  Du Jing-yuan,et al.  Biodegradation of absorbable hydroxyapatite/poly-DL-lactide composites in different environment , 2002 .

[27]  Scott J Hollister,et al.  Mechanical and in vivo performance of hydroxyapatite implants with controlled architectures. , 2002, Biomaterials.

[28]  D. Kirschner Timebomb: The Global Epidemic of Multi-Drug Resistant Tuberculosis , 2001, Nature Medicine.

[29]  Christopher Dye,et al.  Global trends in resistance to antituberculosis drugs. World Health Organization-International Union against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance. , 2001, The New England journal of medicine.

[30]  A Boyde,et al.  Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. , 2000, Journal of biomedical materials research.

[31]  Leland Lou,et al.  Novel drug delivery systems , 1999, Current review of pain.

[32]  D. Wise,et al.  Low-density poly(dl-lactide-co-glycolide) foams for prolonged release of isoniazid , 1996 .

[33]  Emanuel M. Sachs,et al.  Solid free-form fabrication of drug delivery devices , 1996 .

[34]  Yie W. Chien,et al.  Novel Drug Delivery Systems , 1991 .

[35]  C. J. Coulson Molecular Mechanisms Of Drug Action , 1988 .

[36]  R. Collins Atlas of drug reactions , 1986 .

[37]  K. Klemm [Gentamicin-PMMA-beads in treating bone and soft tissue infections (author's transl)]. , 1979, Zentralblatt fur Chirurgie.