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The preliminary performance study of the 3D printing of a tricalcium phosphate scaffold for the loading of sustained release anti-tuberculosis drugs

Abstract

In the surgical treatment of tuberculosis of the bones, excision of the lesion site leaves defects in the bone structure. Recent research has shown benefits for bone tissue support, such as tricalcium phosphate, as regrowth materials. These biocompatible engineering materials have good bone inductivity and biologic mechanical performance. The goal of this study was to evaluate the use of 3D printing, a new technology, to design and build 3-dimensional support structures for use in grafting at lesion sites and for use in embedding the sustained release anti-tuberculosis drugs Rifampin and Isoniazid and determine the in vivo performance of these structures. In addition to mechanical studies, osteogenesis, cell viability, and migration were all observed, using Wistar rat models, to determine the effectiveness of this material as a biological support. The bone support showed good resistance to compression, similar to the spongiest bone tissue, and high porosity. In vivo studies showed that the material had a stable time release of Rifampin and Isoniazid through 90 days and achieved effective killing of the tuberculosis-causing bacteria. Finally, the support allowed for good migration and survival of rat bone marrow mesenchymal stem cells, leading to successful bone regrowth and repair. These results imply that the use of 3D printing of tricalcium phosphate scaffolds for bone excision repair and time-release treatment of tuberculosis shows great promise for future treatment of patients with tuberculosis of the bones.

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References

  1. 1.

    Pigrau-Serrallach C, Rodríguez-Pardo D (2013) Bone and joint tuberculosis. Eur Spine J 22(4):556–566

    Article  Google Scholar 

  2. 2.

    Ye X, Zhen P, Li X et al (2010) Study on preparation and properties of novel anti-TB porous calcium phosphate cement. Orthop J Chin 18(23):1981–1986

    Google Scholar 

  3. 3.

    Gu Y, Chen X, Lee J-H et al (2012) Inkjet printed antibiotic-and calcium-eluting bioresorbable nanocomposite micropatterns for orthopedic implants. Acta Biomater 8(1):424–431

    Article  Google Scholar 

  4. 4.

    Wu W, Zheng Q, Guo X (2010) Experimental Study of a Rifampicine-isoniazid-controlled Release Drug Implant. Chin J Biomed Eng 1:137–143

    Google Scholar 

  5. 5.

    Liu P, Jiang J (2011) High performance liquid chromatagraphy to test rifampin and desacetylrifampin in spinal tuberculosis. J Chin Med Univ 40(7):665–668

    Google Scholar 

  6. 6.

    Li D, Ma Y (2013) Research progresses of drug delivery material in the treatment of osteoaticular tuberculosis. Chin J Antituberc 35(5):25–32

    Google Scholar 

  7. 7.

    Chen Q (2013) Study on the Toxicity of Isoniazide with Various Concentrations on Cultured Osteoblasts in vitro[D]. huazhong university of science and technology 31(3):21–27

    Google Scholar 

  8. 8.

    Guo D, Wu H, Xue G et al (2011) The hepatocyet toxicity and the effect of Isoniazid and Rifampicin on the activities of CYP2E1 and CYP3A in mouse primary hepatocytes. Pham J Chin PLA 27(3):221–223

    Google Scholar 

  9. 9.

    Mao K, Yang Y, Li J et al (2009) Investigation of the histology and interfacial bonding between carbonated hydroxyapatite cement and bone. Biomed Mater 4(4):045003

    Article  Google Scholar 

  10. 10.

    Rihn JA, Kirkpatrick K, Albert TJ (2010) Graft options in posterolateral and posterior interbody lumbar fusion. Spine 35(17):1629–1639

    Article  Google Scholar 

  11. 11.

    Schroeder JE, Mosheiff (2011) Tissue engineering approaches for bone repair: concepts and evidence. Injury 42(6):609–613

    Article  Google Scholar 

  12. 12.

    Sugawara A, Asaoka K, Ding SJ (2013) Calcium phosphate-based cements: clinical needs and recent progress. J Mater Chem B 1(8):1081–1089

    Article  Google Scholar 

  13. 13.

    Dorozhkin SV (2010) Bioceramics of calcium orthophosphates. Biomaterials 31(7):1465–1485

    Article  Google Scholar 

  14. 14.

    Wu C, Chang J (2013) A review of bioactive silicate ceramics. Biomed Mater 8(3):032001

    Article  Google Scholar 

  15. 15.

    Nischang I, Teasdale I, Brüggemann O (2011) Porous polymer monoliths for small molecule separations: advancements and limitations. Anal Bioanal Chem 400(8):2289–2304

    Article  Google Scholar 

  16. 16.

    Lu L, Zhang Q, Wootton D et al (2012) Biocompatibility and biodegradation studies of PCL/β-TCP bone tissue scaffold fabricated by structural porogen method. J Mater Sci 23(9):2217–2226

    Google Scholar 

  17. 17.

    Butscher A, Bohner M, Hofmann S et al (2011) Structural and material approaches to bone tissue engineering in powder-based three-dimensional printing. Acta Biomater 7(3):907–920

    Article  Google Scholar 

  18. 18.

    Wei X, Zhao N, Lin Z et al (2013) Preparation and characterization of three-dimensional porus β-tricalcium phosphate scaffold with controlled porous. J Funct Mater 43(23):3217–3221

    Google Scholar 

  19. 19.

    Bao Y, Zhang W, Wang Y et al (2012) Preparation and release features of long-term slow-release two-component drug artificial bone. Chin J Tissue Eng Res 16(38):7126–7130

    Google Scholar 

  20. 20.

    Karageorgiou V, Kaplan D (2005) Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials 26(27):5474–5491

    Article  Google Scholar 

  21. 21.

    Miranda P, Pajares A, Saiz E et al (2007) Fracture modes under uniaxial compression in hydroxyapatite scaffolds fabricated by robocasting. J Biomed Mater Res Part A 83(3):646–655

    Article  Google Scholar 

  22. 22.

    Miranda P, Pajares A, Guiberteau F (2008) Finite element modeling as a tool for predicting the fracture behavior of robocast scaffolds. Acta Biomater 4(6):1715–1724

    Article  Google Scholar 

  23. 23.

    Bandyopadhyay A, Petersen J, Fielding G et al (2012) ZnO, SiO2, and SrO doping in resorbable tricalcium phosphates: Influence on strength degradation, mechanical properties, and in vitro bone–cell material interactions. J Biomed Mater Res B 100(8):2203–2212

    Article  Google Scholar 

  24. 24.

    Olszta MJ, Cheng X, Jee SS et al (2007) Bone structure and formation: A new perspective. Mater Sci Eng 58(3):77–116

    Article  Google Scholar 

  25. 25.

    Libicher M, Vetter M, Wolf I et al (2005) CT volumetry of intravertebral cement after kyphoplasty. Comparison of polymethylmethacrylate and calcium phosphate in a 12-month follow-up. Eur Radiol 15(8):1544–1549

    Article  Google Scholar 

  26. 26.

    Walsh WR, Vizesi F, Michael D et al (2008) β-TCP bone graft substitutes in a bilateral rabbit tibial defect model. Biomaterials 29(3):266–271

    Article  Google Scholar 

  27. 27.

    Santos CF, Silva AP, Lopes L et al (2012) Design and production of sintered β-tricalcium phosphate 3D scaffolds for bone tissue regeneration. Mater Sci Eng C 32(5):1293–1298

    Article  Google Scholar 

  28. 28.

    Wu Q, Zhang X, Wu B et al (2013) Fabrication and characterization of porous HA/β-TCP scaffolds strengthened with micro-ribs structure. Mater Lett 92:274–277

    Article  Google Scholar 

  29. 29.

    Best S, Porter A, Thian E et al (2008) Bioceramics: past, present and for the future. J Eur Ceram Soc 28(7):1319–1327

    Article  Google Scholar 

  30. 30.

    Cao H, Kuboyama N (2010) A biodegradable porous composite scaffold of PGA/β-TCP for bone tissue engineering. Bone 46(2):386–395

    Article  Google Scholar 

  31. 31.

    Wu S, Liu X, Yeung KW et al (2014) Biomimetic porous scaffolds for bone tissue engineering. Mater Sci Eng 80:1–36

    Article  Google Scholar 

  32. 32.

    Chu X, Zhao P, Sun K et al (2009) Properties research of β-tricalcium phosphate bone cements. J Ceram 3:295–299

    Google Scholar 

  33. 33.

    Bose S, Vahabzadeh S, Bandyopadhyay A (2013) Bone tissue engineering using 3D printing. Mater Today 16(12):496–504

    Article  Google Scholar 

  34. 34.

    Li M, Liu X, Liu X et al (2009) Development of macroporous calcium phosphate cements as bone substitutes by using gelatin microspheres. Orthop J Chin 7:526–529

    Google Scholar 

  35. 35.

    Saifullah B, Hussein M, Hussein Al Ali S (2011) Controlled-release approaches towards the chemotherapy of tuberculosis. Int J Nanomed 7:5451–5463

    Google Scholar 

  36. 36.

    Sweetman SC (2005) Martindale: the extra pharmacopoeia. Pharmaceutical Press, London, pp 1371–1377

    Google Scholar 

  37. 37.

    Rang H, Dale M, Rither J (1999) Drugs used to treat tuberculosis. Pharmacology, 4th edn. Churchill Livingstone, London, pp 703–707

    Google Scholar 

  38. 38.

    Li G, Zhang J, Zhao X et al (2012) Correlation between levels of isoniazid and rifampicin resistance andlargeted gene mutation in mycobacrerium tuberculosis. Chin J Antituberc 34(6):360–365

    Google Scholar 

  39. 39.

    Wang Z, Shi J, Geng G et al (2013) Ultra-short-course chemotherapy for spinal tuberculosis: five years of observation. Eur Spine J 22(2):274–281

    Article  Google Scholar 

  40. 40.

    Bose S, Roy M, Bandyopadhyay A (2012) Recent advances in bone tissue engineering scaffolds. Trends Biotechnol 30(10):546–554

    Article  Google Scholar 

  41. 41.

    Duarte Campos DF, Vogt M, Lindner M et al (2014) Two-photon laser scanning microscopy as a useful tool for imaging and evaluating macrophage-, IL-4 activated macrophage-and osteoclast-based in vitro degradation of beta-tricalcium phosphate bone substitute material. Microsc Res Tech 77(2):143–152

    Article  Google Scholar 

Download references

Acknowledgements

The authors wish to thank the Lanzhou Military Region General Hospital Orthopedics Research Institute and Professor Zhen Ping. This study was funded by the National Natural Sciences Fund (81371983).

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Correspondence to Ping Zhen.

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Yuan, J., Zhen, P., Zhao, H. et al. The preliminary performance study of the 3D printing of a tricalcium phosphate scaffold for the loading of sustained release anti-tuberculosis drugs. J Mater Sci 50, 2138–2147 (2015). https://doi.org/10.1007/s10853-014-8776-0

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Keywords

  • Sustained Release
  • Simulated Body Fluid
  • Scaffold Material
  • Orthogonal Experimental Design
  • Calcium Phosphate Bone Cement