Three-dimensionally plotted MBG/PHBHHx composite scaffold for antitubercular drug delivery and tissue regeneration

A suitable drug-loaded scaffold that can postoperatively release an antituberculosis drug efficiently in a lesion area and help repair a bone defect is very important in the clinical treatment of bone tuberculosis (TB). In this study, a composite drug-loaded cylindrical scaffold was prepared by using three-dimensional printing technology in combination with the mesoporous confinement range, surface chemical groups, and gradual degradation of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate). This achieves the slow release of a drug for as long as possible. We implanted the drug-loaded compound scaffold into New Zealand rabbits’ femur defect model to study the in vivo drug release performance and osteogenic ability. The in vivo release of isoniazid and rifampicin from the prepared composites could be effectively sustained for 12 weeks in local tissues, whereas these drugs were sustained for just 2 weeks in a control group. The blood drug concentrations were very low and most concentrations were below 5 μg/ml. Therefore, the systemic toxic adverse effect is very low. In addition, the composite exhibits good osteogenic potential in a rabbit bone defect model. The results of this study indicate that this composite has great potential for treating osteoarticular TB.

[1]  F. Forriol,et al.  Radiological and histological analysis of cortical allografts: an experimental study in sheep femora , 2004, Archives of Orthopaedic and Trauma Surgery.

[2]  J. Kjems,et al.  Fabrication and characterization of a rapid prototyped tissue engineering scaffold with embedded multicomponent matrix for controlled drug release , 2012, International journal of nanomedicine.

[3]  Gianaurelio Cuniberti,et al.  Three-dimensional printing of hierarchical and tough mesoporous bioactive glass scaffolds with a controllable pore architecture, excellent mechanical strength and mineralization ability. , 2011, Acta biomaterialia.

[4]  A. E. El Haj,et al.  Sustained PDGF-BB release from PHBHHx loaded nanoparticles in 3D hydrogel/stem cell model. , 2015, Journal of biomedical materials research. Part A.

[5]  S. Song,et al.  Simultaneous determination of first-line anti-tuberculosis drugs and their major metabolic ratios by liquid chromatography/tandem mass spectrometry. , 2007, Rapid communications in mass spectrometry : RCM.

[6]  P. Ghosh,et al.  Tuberculous arthritis—the challenges and opportunities: observations from a tertiary center , 2011 .

[7]  F. Forriol,et al.  Effects of preservation on the mechanical strength and chemical composition of cortical bone: an experimental study in sheep femora. , 2002, Biomaterials.

[8]  Xufeng Zhou,et al.  Highly ordered mesoporous bioactive glasses with superior in vitro bone-forming bioactivities. , 2004, Angewandte Chemie.

[9]  G. Khuller,et al.  Sustained release of isoniazid from a single injectable dose of poly (DL-lactide-co-glycolide) microparticles as a therapeutic approach towards tuberculosis. , 2001, International journal of antimicrobial agents.

[10]  Jinku Kim,et al.  Rapid-prototyped PLGA/β-TCP/hydroxyapatite nanocomposite scaffolds in a rabbit femoral defect model , 2012, Biofabrication.

[11]  G. Soma,et al.  Delivery of rifampicin-PLGA microspheres into alveolar macrophages is promising for treatment of tuberculosis. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[12]  Shanshan Huang,et al.  Luminescent and Mesoporous Europium-Doped Bioactive Glasses (MBG) as a Drug Carrier , 2009 .

[13]  H. Terada,et al.  The behavior of PLGA microspheres containing rifampicin in alveolar macrophages. , 2010, Colloids and surfaces. B, Biointerfaces.

[14]  Xiaofeng Chen,et al.  Synthesis and in vitro bioactivity of novel mesoporous hollow bioactive glass microspheres , 2009 .

[15]  María Vallet-Regí,et al.  Ordered Mesoporous Bioactive Glasses for Bone Tissue Regeneration , 2006 .

[16]  Qiong Wu,et al.  Evaluation of three-dimensional scaffolds made of blends of hydroxyapatite and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) for bone reconstruction. , 2004, Biomaterials.

[17]  María Vallet-Regí,et al.  Mesoporous Materials for Drug Delivery , 2008 .

[18]  Su Jin Heo,et al.  Three-Dimensional Mesoporous−Giantporous Inorganic/Organic Composite Scaffolds for Tissue Engineering , 2007 .

[19]  Guoqiang Chen,et al.  The mechanical properties and in vitro biodegradation and biocompatibility of UV-treated poly(3-hydroxybutyrate-co-3-hydroxyhexanoate). , 2006, Biomaterials.

[20]  常江 Well-ordered mesoporous bioactive glasses(MBG):A promising bioactive drug delivery system , 2006 .

[21]  Jianhua Sun,et al.  A programmed release multi-drug implant fabricated by three-dimensional printing technology for bone tuberculosis therapy , 2009, Biomedical materials.

[22]  S. Song,et al.  Method for simultaneous analysis of nine second-line anti-tuberculosis drugs using UPLC-MS/MS. , 2013, The Journal of antimicrobial chemotherapy.

[23]  G. Khuller,et al.  Liposomes and PLG microparticles as sustained release antitubercular drug carriers--an in vitro-in vivo study. , 2001, International journal of antimicrobial agents.

[24]  Alimuddin Zumla,et al.  WHO's 2013 global report on tuberculosis: successes, threats, and opportunities , 2013, The Lancet.