Ribose pre-treatment can protect the fatigue life of γ-irradiation sterilized bone

Abstract

Structural bone allografts are often sterilized with γ-irradiation to decrease infection risk, which unfortunately degrades the bone collagen connectivity, making the bone weak and brittle. In previous studies, we successfully protected the quasi-static mechanical properties of human cortical bone by pre-treating with ribose, prior to irradiation. This study focused on the quasi-static and fatigue tensile properties of ribose treated irradiated sterilized bone allografts. Seventy-five samples were cut from the mid-shaft diaphysis of human femurs into standardized dog-bone shape geometries for quasi-static and fatigue tensile testing. Specimens were prepared in sets of three adjacent specimens. Each set was made of a normal (N), irradiated (I) and ribose pre-treated + irradiation (R) group. The R group was incubated in a 1.2 M ribose solution before γ-irradiation. The quasi-static tensile and decalcified tests were conducted to failure under displacement control. The fatigue samples were tested under cyclic loading (10 Hz, peak stress of 45MP, minimum-to-maximum stress ratio of 0.1) until failure or reaching 10 million cycles. Ribose pre-treatment significantly improved significantly the mechanical properties of irradiation sterilized human bone in the quasi-static tensile and decalcified tests. The fatigue life of the irradiated group was impaired by 99% in comparison to the normal control. Surprisingly, the R-group has significantly superior properties over the I-group and N-group (p < 0.01, p < 0.05) (> 100%). This study shows that incubating human cortical bone in a ribose solution prior to irradiation can indeed improve the fatigue life of irradiation-sterilized cortical bone allografts.

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References

  1. Akkus O, Belaney RM (2005) Sterilization by gamma radiation impairs the tensile fatigue life of cortical bone by two orders of magnitude. J Orthop Res 23:1054–1058. https://doi.org/10.1016/j.orthres.2005.03.003

    Article  PubMed  Google Scholar 

  2. Akkus O, Rimnac CM (2001) Fracture resistance of gamma radiation sterilized cortical bone allografts. J Orthop Res 19:927–934. https://doi.org/10.1016/S0736-0266(01)00004-3

    Article  CAS  PubMed  Google Scholar 

  3. Akkus O, Belaney RM, Das P (2005) Free radical scavenging alleviates the biomechanical impairment of gamma radiation sterilized bone tissue. J Orthop Res 23:838–845. https://doi.org/10.1016/j.orthres.2005.01.007

    Article  PubMed  Google Scholar 

  4. Andreaus UA, Colloca M, Toscano A (2008) Mechanical behaviour of a prosthesized human femur: a comparative analysis between walking and stair climbing by using the finite element method. Biophys Bioeng Lett 1(3):1–15

    Google Scholar 

  5. Attia T, Woodside M, Minhas G et al (2017) Development of a novel method for the strengthening and toughening of irradiation-sterilized bone allografts. Cell Tissue Bank. https://doi.org/10.1007/s10561-017-9634-5

    Article  PubMed  Google Scholar 

  6. Barth HD, Zimmermann EA, Schaible E et al (2011) Characterization of the effects of X-ray irradiation on the hierarchical structure and mechanical properties of human cortical bone. Biomaterials 32:8892–8904. https://doi.org/10.1016/j.biomaterials.2011.08.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Burton B, Gaspar A, Josey D et al (2014) Bone embrittlement and collagen modifications due to high-dose gamma-irradiation sterilization. Bone 61:71–81. https://doi.org/10.1016/j.bone.2014.01.006

    Article  CAS  PubMed  Google Scholar 

  8. Caler WE, Carter DR (1989) Bone creep-fatigue damage accumulation. J Biomech 22:625–635

    Article  CAS  PubMed  Google Scholar 

  9. Carter DR, Caler WE (1985) A cumulative damage model for bone fracture. J Orthop Res 3:84–90. https://doi.org/10.1002/jor.1100030110

    Article  CAS  PubMed  Google Scholar 

  10. Cowin SC (2001) Bone mechanics handbook. CRC Press, Boca Raton

    Book  Google Scholar 

  11. Currey John D (2003) Role of collagen and other organics in the mechanical properties of bone. Osteoporos Int 14(Suppl 5):S29–S36. https://doi.org/10.1007/s00198-003-1470-8

    Article  Google Scholar 

  12. Currey JD, Foreman J, Laketić I et al (1997) Effects of ionizing radiation on the mechanical properties of human bone. J Orthop Res 15:111–117. https://doi.org/10.1002/jor.1100150116

    Article  CAS  PubMed  Google Scholar 

  13. Dziedzic-Goclawska A, Kaminski A, Uhrynowska-Tyszkiewicz I, Stachowicz W (2005) Irradiation as a safety procedure in tissue banking. Cell Tissue Bank 6:201–219. https://doi.org/10.1007/s10561-005-0338-x

    Article  CAS  PubMed  Google Scholar 

  14. Goldberg VM (2008) Biology of bone allograft and clinical applications. In: Pietrzak W (ed) Musculoskeletal tissue regeneration: biological materials and methods. Humana Press, New York, pp 81–92

    Google Scholar 

  15. Hamer AJ, Stockley I, Elson RA (1999) Changes in allograft bone irradiated at different temperatures. J Bone Joint Surg Br 81:342–344

    Article  CAS  PubMed  Google Scholar 

  16. Islam A, Chapin K, Moore E et al (2016) Gamma radiation sterilization reduces the high-cycle fatigue life of allograft bone. Clin Orthop Relat Res 474:827–835. https://doi.org/10.1007/s11999-015-4589-y

    Article  PubMed  Google Scholar 

  17. Kaminski A, Jastrzebska A, Grazka E et al (2012) Effect of gamma irradiation on mechanical properties of human cortical bone: influence of different processing methods. Cell Tissue Bank 13:363–374. https://doi.org/10.1007/s10561-012-9308-2

    Article  CAS  PubMed  Google Scholar 

  18. Kawaguchi S, Hart R (2015) The need for structural allograft biomechanical guidelines. J Am Acad 23:119–125. https://doi.org/10.5435/jaaos-d-14-00263

    Article  Google Scholar 

  19. Lakes RS, Katz JL (1979) Viscoelastic properties of wet cortical bone–II. Relaxation mechanisms. J Biomech 12:679–687

    Article  CAS  PubMed  Google Scholar 

  20. Martelli S, Pivonka P, Ebeling PR (2014) Femoral shaft strains during daily activities: implications for atypical femoral fractures. Clin Biomech 29:869–876. https://doi.org/10.1016/j.clinbiomech.2014.08.001

    Article  Google Scholar 

  21. Martin RB, Burr DB, Sharkey NA, Fyhrie DP (2015) Skeletal tissue mechanics. Springer, Berlin

    Google Scholar 

  22. Mitchell EJ, Stawarz AM, Kayacan R, Rimnac CM (2004) The effect of gamma radiation sterilization on the fatigue crack propagation resistance of human cortical bone. J Bone Jt Surg Am 86-A:2648–2657

    Article  Google Scholar 

  23. Nguyen H, Morgan DAF, Forwood MR (2007) Sterilization of allograft bone: effects of gamma irradiation on allograft biology and biomechanics. Cell Tissue Bank 8:93–105. https://doi.org/10.1007/s10561-006-9020-1

    Article  PubMed  Google Scholar 

  24. Nguyen H, Morgan DAF, Sly LI et al (2008) Validation of 15 kGy as a radiation sterilisation dose for bone allografts manufactured at the Queensland Bone Bank: application of the VDmax 15 method. Cell Tissue Bank 9:139–147. https://doi.org/10.1007/s10561-008-9064-5

    Article  CAS  PubMed  Google Scholar 

  25. Pattin CA, Caler WE, Carter DR (1996) Cyclic mechanical property degradation during fatigue loading of cortical bone. J Biomech 29:69–79

    Article  CAS  PubMed  Google Scholar 

  26. Russell NA, Rives A, Pelletier MH et al (2013) The effect of sterilization on the mechanical properties of intact rabbit humeri in three-point bending, four-point bending and torsion. Cell Tissue Bank 14:231–242. https://doi.org/10.1007/s10561-012-9318-0

    Article  PubMed  Google Scholar 

  27. Salehpour A, Butler DL, Proch FS et al (1995) Dose-dependent response of gamma irradiation on mechanical properties and related biochemical composition of goat bone-patellar tendon-bone allografts. J Orthop Res 13:898–906. https://doi.org/10.1002/jor.1100130614

    Article  CAS  PubMed  Google Scholar 

  28. Sasaki N, Yoshikawa M (1993) Stress relaxation in native and EDTA-treated bone as a function of mineral content. J Biomech 26:77–83

    Article  CAS  PubMed  Google Scholar 

  29. Wang X, Bank RA, TeKoppele JM et al (2000) Effect of collagen denaturation on the toughness of bone. Clin Orthop Relat Res 371:228–239

    Article  Google Scholar 

  30. Wang Z, Vashishth D, Picu RC (2018) Bone toughening through stress-induced non-collagenous protein denaturation. Biomech Model Mechanobiol 17:1–14. https://doi.org/10.1007/s10237-018-1016-9

    Article  Google Scholar 

  31. Willett TL, Burton B, Woodside M et al (2015) γ-Irradiation sterilized bone strengthened and toughened by ribose pre-treatment. J Mech Behav Biomed Mater 44:147–155. https://doi.org/10.1016/j.jmbbm.2015.01.003

    Article  CAS  PubMed  Google Scholar 

  32. Winwood K, Zioupos P, Currey JD et al (2006) Strain patterns during tensile, compressive, and shear fatigue of human cortical bone and implications for bone biomechanics. J Biomed Mater Res A 79:289–297. https://doi.org/10.1002/jbm.a.30796

    Article  CAS  PubMed  Google Scholar 

  33. Woodside M, Willett TL (2016) Elastic–plastic fracture toughness and rising JR-curve behavior of cortical bone is partially protected from irradiation–sterilization-induced degradation by ribose protectant. J Mech Behav Biomed Mater 64:53–64. https://doi.org/10.1016/j.jmbbm.2016.07.001

    Article  CAS  PubMed  Google Scholar 

  34. Zioupos P, Hamer AJ, Zioupos P et al (1999) The role of collagen in the declining mechanical properties of aging human cortical bone. J Biomed Mater Res 4636:108–116. https://doi.org/10.1002/(sici)1097-4636(199905)45

    Article  Google Scholar 

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Acknowledgements

This work was funded by the Canadian Institute of Health Research, the Natural Science and Engineering Research Council of Canada, and scholarships from the University of Toronto Institute for Biomaterials and Biomedical Engineering and Toronto Musculoskeletal Centre. We acknowledge the help of our tissue-banking partner, Mount Sinai Allograft Technologies.

Funding

This study was funded by a Collaborative Health Research Projects Grant from the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada (Application #290075).

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TA: developed the methods, conducted the experiments, analyzed the data and wrote the first draft of the manuscript. MG and TW: devised the study and were granted the funding, supervised the methods development, experiments and data analysis, and finalized the manuscript including critical revision. All authors have read and approved the final submitted manuscript.

Corresponding author

Correspondence to Thomas Willett.

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All authors declare they have no conflict of interest.

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This article does not contain any studies with human participants performed by any of the authors. The use of human tissues was approved by the institutional ethics board of Mount Sinai Hospital (Toronto).

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Attia, T., Grynpas, M. & Willett, T. Ribose pre-treatment can protect the fatigue life of γ-irradiation sterilized bone. Cell Tissue Bank 20, 287–295 (2019). https://doi.org/10.1007/s10561-019-09767-6

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Keywords

  • Bone
  • Allograft
  • γ-Irradiation sterilization
  • Toughness
  • Fatigue
  • Collagen
  • Ribose