Article
Development of a novel in vitro model of osteoporotic bone to examine new biodegradable and osteoinductive bone cement for the management of osteoporotic vertebral fractures
Entwicklung eines ovinen Osteoporose-Modells in vitro zur Erprobung eines neuartigen osteoinduktiven und biodegradierbaren Knochenzementes zur Augmentation von Pedikelschrauben
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Authors
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Harald Krenzlin
- Universitätsmedizin Mainz, Klinik für Neurochirurgie, Mainz, Deutschland
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Andrea Foelger
- Universitätsmedizin Mainz, Klinik für Neurochirurgie, Mainz, Deutschland
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Volker Mailänder
- Max Planck Institute for Polymer Research, Mainz, Deutschland
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Christopher Blase
- Frankfurt University of Applied Sciences, Franfurt/Main, Deutschland
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Sven Kantelhardt
- Universitätsmedizin Mainz, Klinik für Neurochirurgie, Mainz, Deutschland
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Florian Ringel
- Universitätsmedizin Mainz, Klinik für Neurochirurgie, Mainz, Deutschland
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Naureen Keric
- Universitätsmedizin Mainz, Klinik für Neurochirurgie, Mainz, Deutschland
| Published: | June 4, 2021 |
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Outline
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Objective: Osteoporosis is the most common age-related progressive skeletal disease characterized by bone loss and concomitant tendency for osteoporotic vertebral fractures (OVF). The management of OVF often necessitates fusion surgery, with high rates of implant failure due to the brittle bone substance. In vitro models of osteoporosis to test implant pull out strength are scarce. Here we present a novel ovine model of osteoporotic bone to test an new composite osteoinductive and biodegradable bone cement to boost the anti-osteoporotic therapy and improve long term implant integrity.
Methods: 12 sheep vertebrae were perfused with 25% TBD-1 decalcifier solution using a double syringe pump set-up for 24h. Bone density was measured prior and after decalcification using dual-energy X-ray absorptiometry (DEXA). Osteoinductive synthetic collagen I mimetic peptide (P15) was mixed with biodegradable calcium phosphate cement (CaP). Pedicle screws were introduced into one pedicle of each vertebrae and augmented with CaP/P15. Standard polymethylmethacrylate (PMMA) cement and non-augmented screws served as control. Linear pullout testing was performed. Osteoblastic transformation of human mesenchymal stem cells (MES) was verified via osteoblast-related gene expressions of bone-specific alkaline phosphatase2 (ALPII) and osteocalcein using Immunofluorescence and RT-PCR.
Results: Bone marrow density (BMD) prior to decalcification was 0.72±0.02 g/cm2 prior and 0.53±0.04 g/cm2 after decalcification.
BMD was decreased by 28.75±2.6 %. mRNA expression of ALPII increased 32.76±0.212 %, while osteocalcein was increased by 16.15±0.72 % after co-culture of MES with Cap/P15. Immunofluorescent staining was increased in a similar manner.
Biomechanical testing in untreated vertebrae showed pullout loads of 2010±83 NM after augmentation with CaP/P15 compared to 2112±49 NM after augmentation with PMMA and 1405±25 without augmentation. (p < 0.001). In decalcified vertebrae, pullout strength untreated was 827±33 NM and1250±65 NM after augmentation with Cap/P15.
Conclusion: The CaP/P15 composite cement is capable of inducing osteoblastic differentiation in human MES in vitro. The ovine decalcification model provides a similar loss of bone marrow density as expected from osteoporotic vertebrae in vivo and is capable of mimicking the decreased pull out loads of pedicle screws in vitro. Pull out loads of CaP/P15 augmented pedicle screws are superior to controls in our model.
