Skip to main content
Erschienen in: European Journal of Trauma and Emergency Surgery 5/2015

01.10.2015 | Original Article

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

verfasst von: F. Högel, S. Hoffmann, S. Hungerer, E. Fleischacker, T. Ullamann, O. B. Betz, P. Augat

Erschienen in: European Journal of Trauma and Emergency Surgery | Ausgabe 5/2015

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Glassner PJ, Tejwani NC. Failure of proximal femoral locking compression plate: a case series. J Orthop Trauma. 2011;25(2):76–83.CrossRefPubMed Glassner PJ, Tejwani NC. Failure of proximal femoral locking compression plate: a case series. J Orthop Trauma. 2011;25(2):76–83.CrossRefPubMed
2.
Zurück zum Zitat 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 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
3.
Zurück zum Zitat 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. 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.
Zurück zum Zitat 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.PubMed 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.PubMed
5.
Zurück zum Zitat Shirley, et al. Systemic recruitment of osteoblastic cells in fracture healing. J Orthop Res. 2005;23(5):1013–21.CrossRefPubMed Shirley, et al. Systemic recruitment of osteoblastic cells in fracture healing. J Orthop Res. 2005;23(5):1013–21.CrossRefPubMed
6.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
7.
Zurück zum Zitat 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.CrossRef 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.CrossRef
8.
Zurück zum Zitat Krug A. Mikrozirkulation und Sauerstoffversorgung des Gewebes. Phlebologie. 2007;36:300–12. Krug A. Mikrozirkulation und Sauerstoffversorgung des Gewebes. Phlebologie. 2007;36:300–12.
9.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
10.
Zurück zum Zitat Hak, et al. Recombinant human BMP-7 effectively prevents non-union in both young and old rats. J Orthop Res. 2006;1:11–20.CrossRef Hak, et al. Recombinant human BMP-7 effectively prevents non-union in both young and old rats. J Orthop Res. 2006;1:11–20.CrossRef
11.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
12.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
13.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
14.
Zurück zum Zitat 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.CrossRef 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.CrossRef
15.
Zurück zum Zitat 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. 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.
Zurück zum Zitat 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.PubMedCentralCrossRefPubMed 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.PubMedCentralCrossRefPubMed
17.
Zurück zum Zitat 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.PubMedCentralPubMed 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.PubMedCentralPubMed
18.
Zurück zum Zitat 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 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
19.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
20.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
21.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
22.
Zurück zum Zitat 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.CrossRef 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.CrossRef
Metadaten
Titel
Bone healing of critical size defects of the rat femur after the application of bone marrow aspirate and two different rh-BMP7 concentrations
verfasst von
F. Högel
S. Hoffmann
S. Hungerer
E. Fleischacker
T. Ullamann
O. B. Betz
P. Augat
Publikationsdatum
01.10.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Trauma and Emergency Surgery / Ausgabe 5/2015
Print ISSN: 1863-9933
Elektronische ISSN: 1863-9941
DOI
https://doi.org/10.1007/s00068-014-0473-9

Weitere Artikel der Ausgabe 5/2015

European Journal of Trauma and Emergency Surgery 5/2015 Zur Ausgabe

ESTES News 5.2015

ESTES News 5.2015

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.