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Efficacy of two different demineralised bone matrix grafts to promote bone healing in a critical-size-defect: a radiological, histological and histomorphometric study in rat femurs

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Abstract

Purpose

The aim of the study was to compare two different demineralised bone matrices used clinically regarding their ability to induce bone healing in a critical-size-defect rat model.

Methods

We stabilised 4 mm femur defects with a custom-made plate and filled them either with demineralised bone matrix (DBM) or DBX (DBX Putty®). Bone morphogenetic protein 2 (BMP-2)-loaded collagen and an empty defect served as controls. The outcome was followed after 21 and 42 days by radiology (Faxitron; microCT) and histology.

Results

Defect healing did not occur in any animal from the empty control, DBM or DBX group. Residuals of the implanted material were still found after six weeks, but only limited callus formation was visible. In contrast, the BMP-2 control demonstrated enhanced formation of callus tissue and undisturbed healing. After 21 days, 11 out of 16 and after 42 days, 7 out of 8 BMP-2-treated animals showed complete defect bridging by cancellous bone tissue.

Conclusions

Demineralised bone grafts were not capable of defect reconstruction; only BMP-2 was able to provide sufficient stimulus to induce uneventful bridging under the specific experimental conditions.

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References

  1. Fayaz HC et al (2011) The role of stem cells in fracture healing and nonunion. Int Orthop 35:1587–1597

    Article  PubMed Central  PubMed  Google Scholar 

  2. Calori GM, Mazza E, Colombo M, Ripamonti C (2011) The use of bone-graft substitutes in large bone defects: any specific needs? Injury 42(Suppl 2):S56–S63

    Article  PubMed  Google Scholar 

  3. Rogers GF, Greene AK (2012) Autogenous bone graft: basic science and clinical implications. J Craniofacial Surg 23:323–327

    Article  Google Scholar 

  4. Boone DW (2003) Complications of iliac crest graft and bone grafting alternatives in foot and ankle surgery. Foot Ankle Clin 8:1–14

    Article  PubMed  Google Scholar 

  5. Sasso RC, LeHuec JC, Shaffrey C, Spine Interbody Research G (2005) Iliac crest bone graft donor site pain after anterior lumbar interbody fusion: a prospective patient satisfaction outcome assessment. J Spinal Disord Tech 18(Suppl):S77–S81

    Article  PubMed  Google Scholar 

  6. Silber JS et al (2003) Donor site morbidity after anterior iliac crest bone harvest for single-level anterior cervical discectomy and fusion. Spine (Phila Pa 1976) 28:134–139

    Article  Google Scholar 

  7. Gruskin E, Doll BA, Futrell FW, Schmitz JP, Hollinger JO (2012) Demineralized bone matrix in bone repair: history and use. Adv Drug Deliv Rev 64:1063–1077

    Article  CAS  PubMed  Google Scholar 

  8. De Long WG Jr et al (2007) Bone grafts and bone graft substitutes in orthopaedic trauma surgery. A critical analysis. J Bone Joint Surg Am 89:649–658

    Article  PubMed  Google Scholar 

  9. Dinopoulos HT, Giannoudis PV (2006) Safety and efficacy of use of demineralised bone matrix in orthopaedic and trauma surgery. Expert Opin Drug Saf 5:847–866

    Article  CAS  PubMed  Google Scholar 

  10. Blum B, Moseley J, Miller L, Richelsoph K, Haggard W (2004) Measurement of bone morphogenetic proteins and other growth factors in demineralized bone matrix. Orthopedics 27:s161–s165

    PubMed  Google Scholar 

  11. Li H, Pujic Z, Xiao Y, Bartold PM (2000) Identification of bone morphogenetic proteins 2 and 4 in commercial demineralized freeze-dried bone allograft preparations: pilot study. Clin Implant Dent Relat Res 2:110–117

    Article  CAS  PubMed  Google Scholar 

  12. Wildemann B, Kadow-Romacker A, Haas NP, Schmidmaier G (2007) Quantification of various growth factors in different demineralized bone matrix preparations. J Biomed Mater Res A 81:437–442

    Article  CAS  PubMed  Google Scholar 

  13. Wildemann B, Kadow-Romacker A, Pruss A, Haas NP, Schmidmaier G (2007) Quantification of growth factors in allogenic bone grafts extracted with three different methods. Cell Tissue Bank 8:107–114

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Bormann N, Pruss A, Schmidmaier G, Wildemann B (2010) In vitro testing of the osteoinductive potential of different bony allograft preparations. Arch Orthop Trauma Surg 130:143–149

    Article  CAS  PubMed  Google Scholar 

  15. McKay WF, Peckham SM, Badura JM (2007) A comprehensive clinical review of recombinant human bone morphogenetic protein-2 (INFUSE Bone Graft). Int Orthop 31:729–734

    Article  PubMed Central  PubMed  Google Scholar 

  16. Pruss A et al (2001) Validation of the sterilization procedure of allogeneic avital bone transplants using peracetic acid-ethanol. Biologicals 29:59–66

    Article  CAS  PubMed  Google Scholar 

  17. Guldberg RE et al (2004) Functional integration of tissue-engineered bone constructs. J Musculoskelet Neuronal Interact 4:399–400

    CAS  PubMed  Google Scholar 

  18. Einhorn TA, Lane JM, Burstein AH, Kopman CR, Vigorita VJ (1984) The healing of segmental bone defects induced by demineralized bone matrix. A radiographic and biomechanical study. J Bone Joint Surg Am 66:274–279

    CAS  PubMed  Google Scholar 

  19. Gepstein R, Weiss RE, Hallel T (1987) Bridging large defects in bone by demineralized bone matrix in the form of a powder. A radiographic, histological, and radioisotope-uptake study in rats. J Bone Joint Surg Am 69:984–992

    CAS  PubMed  Google Scholar 

  20. Hansen A et al (2001) Demineralized bone matrix-stimulated bone regeneration in rats enhanced by an angiogenic dipeptide derivate. Cell Tissue Bank 2:69–75

    Article  CAS  PubMed  Google Scholar 

  21. Raines AL et al (2011) Hyaluronic acid stimulates neovascularization during the regeneration of bone marrow after ablation. J Biomed Mater Res A 96:575–583

    Article  PubMed  Google Scholar 

  22. Boerckel JD et al (2011) Effects of protein dose and delivery system on BMP-mediated bone regeneration. Biomaterials 32:5241–5251

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Boerckel JD et al (2012) Effects of in vivo mechanical loading on large bone defect regeneration. J Orthop Res 30:1067–1075

    Article  PubMed Central  PubMed  Google Scholar 

  24. Johnson MR, Boerckel JD, Dupont KM, Guldberg RE (2011) Functional restoration of critically sized segmental defects with bone morphogenetic protein-2 and heparin treatment. Clin Orthop Relat Res 469:3111–3117

    Article  PubMed Central  PubMed  Google Scholar 

  25. Wojtowicz AM et al (2010) Coating of biomaterial scaffolds with the collagen-mimetic peptide GFOGER for bone defect repair. Biomaterials 31:2574–2582

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Cornell CN (1999) Osteoconductive materials and their role as substitutes for autogenous bone grafts. Orthop Clin N Am 30:591–598

    Article  CAS  Google Scholar 

  27. Schwarz C et al (2013) Mechanical load modulates the stimulatory effect of BMP2 in a rat nonunion model. Tissue Eng Part A 19:247–254

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Schutzenberger S et al (2012) The optimal carrier for BMP-2: a comparison of collagen versus fibrin matrix. Arch Orthop Trauma Surg 132:1363–1370

    Article  PubMed  Google Scholar 

  29. Yasuda H et al (2012) Repair of critical long bone defects using frozen bone allografts coated with an rhBMP-2-retaining paste. J Orthop Sci 17:299–307

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors gratefully thank Prof. Robert E. Guldberg (Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA) and his former co-worker Joel D. Boerckel, PhD, for providing detailed information on the segmental defect model and technical drawings of the fixation device. Sincere thanks to Anke Kadow-Romacker for her help analysing microCT data and to Bettina Willie, PhD, for correcting grammar and spelling. This study was supported by the BMBF (BCRT, FKZ 1315848A).

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Correspondence to Britt Wildemann.

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Fassbender, M., Minkwitz, S., Thiele, M. et al. Efficacy of two different demineralised bone matrix grafts to promote bone healing in a critical-size-defect: a radiological, histological and histomorphometric study in rat femurs. International Orthopaedics (SICOT) 38, 1963–1969 (2014). https://doi.org/10.1007/s00264-014-2321-2

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  • DOI: https://doi.org/10.1007/s00264-014-2321-2

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