Artikel
Strontium enhances BMP-2 mediated bone regeneration in a femoral murine bone defect model
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Autoren
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Stefan Zwingenberger
- UniversitätsCentrum für Orthopädie und Unfallchirurgie an der Technischen Universität Dresden, Dresden, Germany
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Saskia Schlootz
- UniversitätsCentrum für Orthopädie und Unfallchirurgie an der Technischen Universität Dresden, Dresden, Germany
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Mandy Quade
- Zentrum für Translationale Knochen-, Gelenk- und Weichgewebeforschung an der Technischen Universität Dresden, Dresden, Germany
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Maik Stiehler
- UniversitätsCentrum für Orthopädie und Unfallchirurgie an der Technischen Universität Dresden, Dresden, Germany
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Klaus-Peter Günther
- UniversitätsCentrum für Orthopädie und Unfallchirurgie an der Technischen Universität Dresden, Dresden, Germany
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Klaus-Dieter Schaser
- UniversitätsCentrum für Orthopädie und Unfallchirurgie an der Technischen Universität Dresden, Dresden, Germany
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Stuart B. Goodman
- Department of Orthopaedic Surgery, Stanford University, Redwood City, United States
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Michael Gelinsky
- Zentrum für Translationale Knochen-, Gelenk- und Weichgewebeforschung an der Technischen Universität Dresden, Dresden, Germany
| Veröffentlicht: | 10. Oktober 2016 |
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Gliederung
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Objectives: Osteoporosis, a disease characterized by reduced bone density and quality, causes more than 8.9 million fractures annually worldwide. Due to its ability to inhibit bone resorption while simultaneously enhancing bone formation, strontium (Sr), is one clinical treatment option for osteoporosis. Since high dose systemic administration of strontium ranelate may lead to severe side effects like osteomalacia or an increased risk of myocardial infarction, a controlled local release of strontium ions might be preferable in the treatment of bone defects. In our present study, we investigated the bone regenerative potential of strontium modified mineralized collagen type 1 matrix (MCM) scaffolds in combination with (or without) the potent osteogenic growth factor bone morphogenetic protein 2 (BMP-2) in a murine segmental bone defect model.
Methods: During production of the MCM-scaffolds (cylinders: 2 mm diameter, 2 mm height) calcium chloride was substituted by 0, 50 or 100% strontium chloride. Sr 0 and Sr 100 scaffolds were additionally functionalized with 75 mg heparin and loaded with 2.5 µg rhBMP-2. Sixty five 12-week-old nu/nu nude mice were randomized to 5 groups (Sr 0, Sr 50, Sr 100, Sr 0 + BMP-2 and Sr 100 + BMP-2). Bone defects of 2 mm length were created in the right femur and stabilized by an external fixator. MCM scaffolds were implanted at the defect site. After 6 weeks animals were euthanized and biomechanical 3-point-bending tests were performed. Thereafter, microcomputed tomography (µCT)-scans were done to analyze the regenerated bone volume. For histomorphological investigations, hematoxylin and eosin staining was performed. All experiments were approved by the Local Animal Care Committee of Dresden University Hospital (protocol no. 24-9168.11-1/2013-75).
Results and Conclusion: The complete strontium substitution (Sr 100) enhanced the bending stiffness as compared to 0% strontium (Sr 100 + BMP-2: 6.1 ± 1.7 N vs. Sr 0 + BMP-2: 4.2 ± 2.0 N, p = 0.0227). The combination of Sr 0 and BMP-2 (7.7 ± 1.4 mm3) as well as Sr 100 and BMP-2 (8.2 ± 1.3 mm3) significantly increased the regenerated bone volume compared to the groups without BMP-2 (Sr 0: 5.5 ± 1.2 mm³, Sr 50: 5.5 ± 1.2 mm3, Sr 100: 6.3 ± 1.5 mm3). Regardless of the strontium content, scaffolds loaded with BMP-2 (Sr 0 + BMP-2: 8.7 ± 1.3, Sr 100 + BMP-2: 9.3 ± 0.7) significantly increased the histological degree of healing of the defect compared to scaffolds without BMP-2 (Sr 0: 2.0 ± 1.5, Sr 50: 2.2 ± 1.1, Sr 100: 2.5 ± 1.4). Interestingly, significant differences were also observed between Sr 0 + BMP-2 and Sr 100 + BMP-2 (p < 0.0001) as well as Sr 0 and Sr 100 (p < 0.05).
Our study confirmed that, in a segmental bone defect, BMP-2 mediated bone regeneration can be enhanced by strontium modified scaffolds. Combining BMP-2 and strontium release from MCM scaffolds is a promising strategy to enhance bone regeneration, especially in patients suffering from osteoporosis.
