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| Motta, Antonella |
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| Mohamed, Tarek |
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| Ertürk, Emre |
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| Taccardi, Nicola |
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| Petrov, R. H. | Madrid |
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Tempfer, Herbert
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article
Synergistic effect of umbilical cord extracellular vesicles and rhBMP-2 to enhance the regeneration of a metaphyseal femoral defect in osteoporotic rats
Abstract
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The aim of this study was to evaluate potential synergistic effects of a single, local application of human umbilical cord MSC-derived sEVs in combination with a low dose of recombinant human rhBMP-2 to promote the regeneration of a metaphyseal femoral defect in an osteoporotic rat model.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>6 weeks after induction of osteoporosis by bilateral ventral ovariectomy and administration of a special diet, a total of 64 rats underwent a distal femoral metaphyseal osteotomy using a manual Gigli wire saw. Defects were stabilized with an adapted Y-shaped mini-locking plate and were subsequently treated with alginate only, or alginate loaded with hUC-MSC-sEVs (2 × 10<jats:sup>9</jats:sup>), rhBMP-2 (1.5 µg), or a combination of sEVs and rhBMP-2 (<jats:italic>n</jats:italic> = 16 for each group). 6 weeks post-surgery, femora were evaluated by µCT, descriptive histology, and biomechanical testing.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Native radiographs and µCT analysis confirmed superior bony union with callus formation after treatment with hUC-MSC-sEVs in combination with a low dose of rhBMP-2. This finding was further substantiated by histology, showing robust defect consolidation 6 weeks after treatment. Torsion testing of the explanted femora revealed increased stiffness after application of both, rhBMP-2 alone, or in combination with sEVs, whereas torque was only significantly increased after treatment with rhBMP-2 together with sEVs.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The present study demonstrates that the co-application of hUC-MSC-sEVs can improve the efficacy of rhBMP-2 to promote the regeneration of osteoporotic bone defects.</jats:p></jats:sec>