Abstract

BackgroundReconstruction materials currently used in clinical for osteoarticular tuberculosis (TB) are unsatisfactory due to a variety of reasons. Rifampicin (RFP) is a well-known and highly effective first-line anti-tuberculosis (anti-TB) drug. Poly-DL-lactide (PDLLA) and nano-hydroxyapatite (nHA) are two promising materials that have been used both for orthopedic reconstruction and as carriers for drug release. In this study we report the development of a novel anti-TB implant for osteoarticular TB reconstruction using a combination of RFP, PDLLA and nHA.MethodsRFP, PDLLA and nHA were used as starting materials to produce a novel anti-TB activity implant by the solvent evaporation method. After manufacture, the implant was characterized and its biodegradation and drug release profile were tested. The in vitro cytotoxicity of the implant was also evaluated in pre-osteoblast MC3T3-E1 cells using multiple methodologies.ResultsA RFP/PDLLA/nHA composite was successfully synthesized using the solvent evaporation method. The composite has a loose and porous structure with evenly distributed pores. The production process was steady and no chemical reaction occurred as proved by Fourier Transform Infrared Spectroscopy (FTIR) and X-Ray Diffraction (XRD). Meanwhile, the composite blocks degraded and released drug for at least 12 weeks. Evaluation of in vitro cytotoxicity in MC3T3-E1 cells verified that the synthesized composite blocks did not affect cell growth and proliferation.ConclusionIt is feasible to manufacture a novel bioactive anti-TB RFP/PDLLA/nHA composite by the solvent evaporation method. The composite blocks showed appropriate properties such as degradation, drug release and biosafety to MC3T3-E1 cells. In conclusion, the novel composite blocks may have great potential for clinical applications in repairing bone defects caused by osteoarticular TB.

Highlights

  • Tuberculosis (TB) is a chronic, debilitating disease caused by Mycobacterium tuberculosis,and is the leading cause of death from a curable infectious disease [1]

  • Titanium mesh, which has been widely used in spinal TB in recent years, provides immediate stability and high mechanical strength; the high prosthesis subsidence ratio and the ease of bacterial adhesion to the titanium mesh surface has resulted in increased recurrence of spinal TB and a poor bone fusion ratio [5]

  • Fourier Transform Infrared Spectroscopy (FTIR) was used to detect the varieties of chemical groups in fabrication process

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Summary

Introduction

Tuberculosis (TB) is a chronic, debilitating disease caused by Mycobacterium tuberculosis,and is the leading cause of death from a curable infectious disease [1]. During the past 10 years, with the overall increase in cases of TB, the incidence of both global spinal TB and drug-resistant spinal TB has significantly increased. The reconstruction implants used in osteoarticular TB include autogenous bone, allograft bone, and artificially synthesized biomaterials including calcium phosphate-based biocement materials, titanium mesh, and polymethylmethacrylate (PMMA). All of these materials have clinical limitations. The recurrence rate of postoperative spinal TB remains as high as 13–26% [6]; it is critically important to develop novel, ideal reconstruction materials for osteoarticular TB. In this study we report the development of a novel anti-TB implant for osteoarticular TB reconstruction using a combination of RFP, PDLLA and nHA

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