gms | German Medical Science

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2015)

20.10. - 23.10.2015, Berlin

SDF-1 alpha enhances bone regeneration induced by low dose BMP-2 in a critical size segmental bone defect

Meeting Abstract

  • presenting/speaker Stefan Zwingenberger - UniversitätsCentrum für Orthopädie und Unfallchirurgie, Technische Universität Dresden, Dresden, Germany
  • Robert Langanke - UniversitätsCentrum für Orthopädie und Unfallchirurgie, Technische Universität Dresden, Dresden, Germany
  • Corina Vater - Zentrum für Translationale Knochen-, Gelenk- und, Weichgewebeforschung, Technische Universität Dresden, Dresden, Germany
  • Stefan Rammelt - UniversitätsCentrum für Orthopädie und Unfallchirurgie, Technische Universität Dresden, Dresden, Germany
  • Michael Gelinsky - Zentrum für Translationale Knochen-, Gelenk- und, Weichgewebeforschung, Technische Universität Dresden, Dresden, Germany
  • Klaus-Peter Günther - UniversitätsCentrum für Orthopädie und Unfallchirurgie, Technische Universität Dresden, Dresden, Germany
  • Stuart B. Goodman - Department of Orthopaedic Surgery, Stanford University, Redwood City, United States
  • Maik Stiehler - UniversitätsCentrum für Orthopädie und Unfallchirurgie, Technische Universität Dresden, Dresden, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2015). Berlin, 20.-23.10.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. DocSA35-502

doi: 10.3205/15dkou541, urn:nbn:de:0183-15dkou5416

Veröffentlicht: 5. Oktober 2015

© 2015 Zwingenberger et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objectives: Critical size bone defects represent a major socioeconomic problem. The growth factor bone morphogenetic protein 2 (BMP-2) is clinically established, however there has been an increasing number of clinical reports concerning severe side effects of BMP-2 used at unphysiological high local doses. In our previous study, we showed that the cytokine stromal derived factor-1 alpha (SDF-1) enhanced BMP-2 mediated bone healing.

The aim of this study was to evaluate the bone regenerative potential of BMP-2/SDF-1 functionalized biomimetic mineralized collagen type I matrix (MCM) scaffolds in a murine segmental critical size defect model in order to reduce the locally required dose of BMP-2.

Methods: Forty-four 12-week-old nu/nu nude mice were randomized to 4 groups (control group, low dose BMP-2 group, low dose BMP-2 + SDF-1 group and high dose BMP-2 group).

MCM scaffolds were functionalized with 75 mg heparin per 1 g collagen. MCM cylinders (2 mm diameter x 3 mm height) were loaded with 15 µL phosphate buffered saline containing 0, 2.5, or 15 µg rhBMP-2 and were incubated for 24 h. Additionally scaffolds for one group were loaded with a combination of 2.5 µg rhBMP-2 and 10 µg human SDF-1.

Critical size bone defects of 3 mm length were created at the right femur of each mouse and stabilized by an external fixator. Control and treatment groups received plain MCM scaffolds and MCM scaffolds loaded with BMP-2 or BMP-2 and SDF-1. After 6 weeks animals were euthanized and µCT-scans were done on each femur to analyze regenerated bone volume. For histomorphology, hematoxylin and eosin staining was performed. The degree of healing of the defect was evaluated using a scale ranging from fibrous tissue only (grade 0) to woven bone (grade 10).

Results and Conclusion: Forty-three out of 44 animals survived the surgical procedure and the observation time. The combination of low dose BMP-2 and SDF-1 (5.8±0.6 mm³, p=0.0479, unpaired t-test) as well as high dose BMP-2 (6.5±0.7 mm³, p=0.008,) significantly increased the regenerated bone volume compared to the control group (4.2±0.5 mm³). Histological analysis showed that low dose BMP-2 (mean grade 6.8±0.3, p<0.0001), low dose BMP-2 + SDF-1 (7.7±0.3, p<0.0001) and high dose BMP-2 (8.0±0.1, p<0.0001) significantly increased the degree of healing of the defect compared to the control (5.2±0.2). There were also significant differences between low dose BMP-2 and low dose BMP-2 + SDF-1 group (p<0.0296) as well as between low dose BMP-2 and high does BMP-2 group (p<0.0003).

Our study confirmed that in a critical size segmental bone defect, the osteoinductive potential of a low local concentration of BMP-2 can be significantly enhanced in the presence of SDF-1, comparable to the regenerative potential of a high BMP-2 concentration at the defect site. Combining BMP-2 and SDF-1 release from MCM scaffolds is a promising strategy to enhance bone regeneration and to avoid severe side effects of high BMP-2 doses.