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Bone healing of critical size defects of the rat femur after the application of bone marrow aspirate and two different rh-BMP7 concentrations

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European Journal of Trauma and Emergency Surgery Aims and scope Submit manuscript

Abstract

Background

It is known that the application of growth factors can enhance fracture healing in defect fractures. The role of bone marrow aspirate (BMA) in combination with BMP-7 and the dosage of rh BMP-7 are still under discussion. Our hypothesis was that the combination of rh-BMP-7 with BMA can heal bone defects more effectively than rh-BMP-7 alone.

Methods

Twenty-eight rats obtained a 5 mm critical size defect in the diaphysis of the right femur which was stabilized by a plate. Rh-BMP-7 was applied at 10 and 200 µg either with collagen or together with collagen and BMA. Collagen only and collagen with BMA served as control groups. Blood flow was assessed by laser Doppler flowmetry in regular time intervals until euthanasia. Callus formation and bone density were measured by micro-computed tomography and biomechanical stability was evaluated by torsional testing at 4 weeks, postoperatively.

Results

Blood flow increased at the operated side after surgery until the second postoperative week independent of treatment. Animals treated with high dose BMP-7 showed significantly (p = 0.001) increased mechanical stiffness independent of BMA treatment. Failure loads were lowest for the two control groups (p = 0.001). The reduction of the BMP-7 dose led to less callus tissue and lower biomechanical stability. BMA did not show significant influence on bone healing.

Conclusion

The combination of an rhBMP-7 dose that would be equivalent to a dose used clinically in humans with bone marrow aspirate does not heal a critical bone defect more effectively than the same rhBMP-7 dose alone.

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References

  1. Glassner PJ, Tejwani NC. Failure of proximal femoral locking compression plate: a case series. J Orthop Trauma. 2011;25(2):76–83.

    Article  PubMed  Google Scholar 

  2. Friedlaender GE, Perry CR, Cole JD, Cook SD, Cierny G, Muschler GF, Zych GA, Calhoun JH, LaForte AJ, Yin S. Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am. 2001;83(Suppl 1(Pt2)):S151–8.

    PubMed  Google Scholar 

  3. Alm JJ, Koivu HM, Heino TJ, Hentunen TA, Laitinen S, Aro HT. Circulating plastic adherent mesenchymal stem cells in aged hip fracture patients. J Orthop Res. 2010;28(12):1634–42. doi:10.1002/jor.21167.

  4. Duan X, Yang L, Zhou Y, Xin Y, Li Q. Application of enhanced green fluorescent protein labeling technology to monitoring marrow mesenchymal stem cells migration after bone fracture. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2006;20(2):102–6.

    CAS  PubMed  Google Scholar 

  5. Shirley, et al. Systemic recruitment of osteoblastic cells in fracture healing. J Orthop Res. 2005;23(5):1013–21.

    Article  PubMed  Google Scholar 

  6. Xiao, et al. Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells. J Bone Miner Res. 2002;17(1):101–10.

    Article  CAS  PubMed  Google Scholar 

  7. Burastero, et al. Association of ex vivo expanded human mesenchymal stem cells and rhBMP-7 is highly effective in treating critical femoral defects in rats. J Orthop Traumatol. 2007;8:49–54.

    Article  Google Scholar 

  8. Krug A. Mikrozirkulation und Sauerstoffversorgung des Gewebes. Phlebologie. 2007;36:300–12.

    Google Scholar 

  9. Chen, et al. Osteogenic protein-1 induced bone formation in an infected segmental defect in the rat femur. J Orthop Res. 2002;20:142–50.

    Article  CAS  PubMed  Google Scholar 

  10. Hak, et al. Recombinant human BMP-7 effectively prevents non-union in both young and old rats. J Orthop Res. 2006;1:11–20.

    Article  Google Scholar 

  11. van den Heuvel MG, Mermans JF, Ambergen AW, van der Hulst RR. Perfusion of the deep inferior epigastric perforator flap measured by laser Doppler imager. Ann Plast Surg. 2011;66(6):648–53.

    Article  PubMed  Google Scholar 

  12. Melnyk M, Henke T, Claes L, Augat P. Revascularisation during fracture healing with soft tissue injury. Arch Orthop Trauma Surg. 2008;128(10):1159–65.

    Article  PubMed  Google Scholar 

  13. Richards RR, Schemitsch EH. Effects of muscle flap coverage on blood flow following devascularisation of a segment of tibia: an experimental investigation in the dog. J Orthop Res. 1989;7:550–8.

    Article  CAS  PubMed  Google Scholar 

  14. Chen X, Schmidt AH, Tsukayama DT, Bourgeault CA, Lew WD. Recombinant human osteogenic protein-1 induces bone formation in a chronically infected, internally stabilized segmental defect in the rat femur. J Bone Joint Surg (Am). 2006;88-A(7):1510–23.

    Article  Google Scholar 

  15. Liao JC, Tzeng ST, Keorochana G, Lee KB, Johnson JS, Morishita Y, Murray SS, Wang JC. Enhancement of recombinant human BMP-7 bone formation with BMP binding peptide in a rodent femoral defect model. J Orthop Res. 2011: 753–759.

  16. Khosla S, Westendorf JJ, Modder UI. Concise review: insights from normal bone remodeling and stem cell-based therapies for bone repair. Stem Cells. 2010;28(12):2124–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Lu C, Xing Z, Yu YY, Colnot C, Miclau T, Marcucio RS. Recombinant human bone morphogenetic protein-7 enhances fracture healing in an ischemic environment. J Orthop Res. 2010;28(5):687–96.

    PubMed Central  CAS  PubMed  Google Scholar 

  18. Xu B, Cui L, Chen W, Wei T, Wu T. Effects of DanShenGuBao on biomechanical properties and bone mineral density of femur induced by retinoic acid in rats. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2010;27(2):307–10.

    PubMed  Google Scholar 

  19. Dawson JI, Smith JO, Aarvold A, Ridgway JN, Curran SJ, Dunlop DG, Oreffo RO. Enhancing the osteogenic efficacy of human bone marrow aspirate: concentrating osteoprogenitors using wave-assisted filtration. Cytotherapy. 2013;15(2):242–52.

    Article  CAS  PubMed  Google Scholar 

  20. Thoesen MS, Berg-Foels WS, Stokol T, Rassnick KM, Jacobson MS, Kevy SV, Todhunter RJ. Use of a centrifugation-based, point-of-care device for production of canine autologous bone marrow and platelet concentrates. Am J Vet Res. 2006;67(10):1655–61.

    Article  PubMed  Google Scholar 

  21. Bae HW, Zhao L, Kanim LE, Wong P, Marshall D, Delamarter RB. Bone marrow enhances the performance of rhBMP-2 in spinal fusion: a rodent model. J Bone Joint Surg Am. 2013;95(4):338–47.

    Article  PubMed  Google Scholar 

  22. Nagata MJ, Santinoni CS, Pola NM, de Campos N, Messora MR, Bomfim SR, Ervolino E, Fucini SE, Faleiros PL, Garcia VG, Bosco AF. Bone marrow aspirate combined with low-level laser therapy: a new therapeutic approach to enhance bone healing. J Photochem Photobiol B. 2013;121:6–14. doi:10.1016/j.jphotobiol.2013.01.013.

    Article  Google Scholar 

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Acknowledgment

The institution of one of the authors (PA) has received, during the study period, funding from Stryker Biotech (Switzerland).

Conflict of interest

The authors Högel F, Hoffmann S, Hungerer S, Fleischacker E, Ullamann T, Betz O.B, Augat P declare no conflict of interest.

Ethical standards

According to the ethical requirements this experiment was approved by the ethical committee of the “Regierung of Oberbayern” (Number: 55.2-1-54-2531-13-10).

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Correspondence to F. Högel.

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Högel, F., Hoffmann, S., Hungerer, S. et al. Bone healing of critical size defects of the rat femur after the application of bone marrow aspirate and two different rh-BMP7 concentrations. Eur J Trauma Emerg Surg 41, 557–563 (2015). https://doi.org/10.1007/s00068-014-0473-9

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  • DOI: https://doi.org/10.1007/s00068-014-0473-9

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