title: Preparation, characterization, and in vitro cytotoxicity evaluation of a novel anti-tuberculosis reconstruction implant.
abstract: BACKGROUND
  Reconstruction 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.
  
  
  METHODS
  RFP, 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  It 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.
authors.affiliation: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, P.R. China; Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: JunFeng
authors.initials: J
authors.lastname: Dong
authors.affiliation: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, P.R. China; Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: ShengMin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, P.R. China; Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: HaoMing
authors.initials: H
authors.lastname: Liu
authors.affiliation: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: YingYing
authors.initials: Y
authors.lastname: Du
authors.affiliation: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: YongHui
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004339:Drug Compounding / Q000379:methods; D004343:Drug Implants; D017886:Durapatite / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D053761:Nanocomposites / Q000737:chemistry / Q000648:ultrastructure; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D016062:Porosity; D012293:Rifampin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D014394:Tuberculosis, Osteoarticular / Q000188:drug therapy; D014961:X-Ray Diffraction
chemical_list: D000995:Antitubercular Agents; D004343:Drug Implants; D011091:Polyesters; C033616:poly(lactide); D017886:Durapatite; D012293:Rifampin
references.citation: Spine J. 2003 Mar-Apr;3(2):130-45
references.pmid: 14589227
references.citation: J Biomed Mater Res. 2001;58(4):335-43
references.pmid: 11410890
references.citation: J Control Release. 2012 Sep 28;162(3):492-501
references.pmid: 22902589
references.citation: J Antimicrob Chemother. 2000 Oct;46(4):571-6
references.pmid: 11020254
references.citation: Eur Spine J. 2008 Nov;17(11):1482-7
references.pmid: 18795341
references.citation: Eur J Pharm Biopharm. 2010 Nov;76(3):366-70
references.pmid: 20816957
references.citation: Bull World Health Organ. 2005 Nov;83(11):857-65
references.pmid: 16302043
references.citation: Antimicrob Agents Chemother. 2011 Apr;55(4):1527-32
references.pmid: 21282447
references.citation: J Mater Sci Mater Med. 2008 Mar;19(3):1075-82
references.pmid: 17701303
references.citation: Acta Biomater. 2011 Nov;7(11):3813-28
references.pmid: 21784182
references.citation: J Biomed Mater Res B Appl Biomater. 2007 Apr;81(1):185-93
references.pmid: 16924605
references.citation: Biofouling. 2011 Feb;27(2):207-15
references.pmid: 21279860
references.citation: J Biomed Mater Res A. 2007 Jun 15;81(4):930-8
references.pmid: 17252547
references.citation: J Mater Sci Mater Med. 1999 Apr;10(4):199-204
references.pmid: 15348151
references.citation: Clin Infect Dis. 2011 May;52(9):e194-9
references.pmid: 21467012
references.citation: Mater Sci Eng C Mater Biol Appl. 2013 Jul 1;33(5):2620-5
references.pmid: 23623076
references.citation: Int J Antimicrob Agents. 2007 May;29(5):593-6
references.pmid: 17317111
references.citation: Int Orthop. 2012 Feb;36(2):285-92
references.pmid: 21720864
references.citation: Int J Mol Sci. 2011 Jan 25;12(2):890-904
references.pmid: 21541032
references.citation: Med Mal Infect. 2012 Sep;42(9):414-20
references.pmid: 22944286
references.citation: J Biomed Mater Res A. 2005 Dec 1;75(3):567-79
references.pmid: 16094665
references.citation: Mater Sci Eng C Biomim Supramol Syst. 2006 Sep;26(8):1289-1295
references.pmid: 26301264
references.citation: J Control Release. 2003 Oct 30;92(3):227-31
references.pmid: 14568403
references.citation: Biomaterials. 2000 May;21(9):889-98
references.pmid: 10735465
references.citation: Clin Orthop Relat Res. 2007 Jul;460:39-49
references.pmid: 17438468
references.citation: J Biomed Mater Res B Appl Biomater. 2009 Feb;88(2):530-43
references.pmid: 18698626
references.citation: J Mater Sci Mater Med. 2011 Nov;22(11):2413-27
references.pmid: 21918894
references.citation: Biomed Mater Eng. 2005;15(5):333-9
references.pmid: 16179753
references.citation: J Mech Behav Biomed Mater. 2013 Jun;22:41-50
references.pmid: 23639839
references.citation: Ann Vasc Surg. 2007 Sep;21(5):603-10
references.pmid: 17823042
references.citation: J Spinal Cord Med. 2011;34(5):440-54
references.pmid: 22118251
references.citation: Physiol Res. 2010;59(3):309-322
references.pmid: 19681662
references.citation: Expert Opin Drug Deliv. 2014 Mar;11(3):299-305
references.pmid: 24328922