Artikel
GDF5 significantly augments the bone formation induced by an injectable, PLGA-fiber reinforced, brushite-forming cement in a sheep defect model of lumbar osteopenia
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Autoren
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Francesca Gunnella
- Waldkrankenhaus "Rudolf Elle" GmbH, AG Experimentelle Rheumatologie, Lehrstuhl für Orthopädie, Universitätsklinikum Jena, Eisenberg, Germany
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Elke Kunisch
- Waldkrankenhaus "Rudolf Elle" GmbH, AG Experimentelle Rheumatologie, Lehrstuhl für Orthopädie, Universitätsklinikum Jena, Eisenberg, Germany
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Stefan Mänz
- Lehrstuhl Materialwissenschaft , Otto-Schott-Institut für Materialforschung, FSU Jena, Jena, Germany
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Bernhard Illerhaus
- Abteilung 8 Zerstörungsfreie Prüfung, Fachgruppe 8.5 Mikro-ZfP, Bundesanstalt für Materialforschung und -prüfung, Berlin, Germany
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Matthias Bungartz
- Waldkrankenhaus "Rudolf-Elle" GmbH, Eisenberg, Germany
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Olaf Brinkmann
- Waldkrankenhaus "Rudolf-Elle" GmbH, Eisenberg, Germany
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Jörg Bossert
- Friedrich-Schiller-Universität Jena, Institut für Materialwissenschaften, Jena, Germany
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Raimund W. Kinne
- Waldkrankenhaus "Rudolf Elle" GmbH, AG Experimentelle Rheumatologie, Lehrstuhl für Orthopädie der FSU Jena, Eisenberg, Germany
| Veröffentlicht: | 23. Oktober 2017 |
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Gliederung
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Objectives: Injectable calcium phosphate cements (CPC) represent resorbable, bioactive, osteoconductive alternatives to bioinert polymethylmethacrylate cement in the treatment of osteoporotic vertebral fractures. To improve their regenerative potential, CPC can be loaded with bone specific growth factors, e.g. bone morphogenic proteins such as growth/differentiation factor-5 (GDF-5). The present study assessed the influence of a newly developed, GDF5-loaded, fiber-reinforced, biodegradable, injectable CPC on bone regeneration in a minimally-invasive, in vivo vertebroplasty model in the lumbar spine of sheep.
Methods: Bone defects (diameter 5 mm) were placed in aged, osteopenic female sheep, treated with poly(l-lactide-co-glycolide acid)-fiber-reinforced, brushite-forming CPC without (L4) or with GDF5 (L5; 1, 5, 100, and 500 μg GDF5; n=5-6 each), and compared with an untouched control (L1). Three and nine months post-operation, effects of CPC±GDF5 were documented by osteodensitometry, histomorphometry, micro-CT, and biomechanical testing.
Results: Compared to untouched controls, CPC±GDF5 numerically or significantly improved all parameters at 3 and 9 months (effects 9 < 3 months for selected parameters). Significant effects of GDF5 were demonstrated for bone mineral density (BMD); bone volume/total volume (BV/TV; micro-CT and histomorphometry), trabecular thickness (Tb.Th), and Tb.N; mineralized surface/bone surface (MS/BS). Dose-dependence of GDF5 at 3 and/or 9 months was focused between 5 and 100 μg GDF5 (BMD; BV/TV (histomorphometry), Tb.Th, and Tb.N; osteoid volume/bone volume, osteoid surface/bone surface, osteoid thickness; MS/BS). Local GDF5 (≤ 100 μg) significantly enhanced the bone formation induced by CPC+fibers for at least 3 months.There were no signs of inflammatory infiltration close to or distant from the injection channel in either L4 or L5 at any time point.
Conclusion: GDF5-loaded CPC showed high biocompatibility (no signs of inflammatory infiltration) and enhanced the bone formation induced by a PLGA-fiber-reinforced CPC in sheep lumbar osteopenia with middle to long-term effects after a single therapeutic application. The results indicated that a local dose of ≤100 μg GDF5 (i.e., 30 to 120-fold less than currently used in the clinic) may be sufficient for bone induction. The novel GDF5-loaded CPC may thus be suitable to replace polymethylacrylate cements for the vertebroplasty/kyphoplasty of osteoporotic vertebral fractures.
