Artikel
Development of a novel in vitro model of osteoporotic bone to examine a new biodegradable and osteoinductive bone cement for the management of osteoporotic vertebral fractures
Entwicklung eines ovinen in vitro Wirbelkörper-Osteoporosemodells zur Untersuchung eines neuen bioresorbierbaren und osteoinduktiven Knochenzementes zur Versorgung osteoporotischer Wirbelkörperfrakturen
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Autoren
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Harald Krenzlin
- Universitätsmedizin Mainz, Neurochirurgische Klinik, Mainz, Deutschland
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Andrea Foelger
- Universitätsmedizin Mainz, Neurochirurgische Klinik, Mainz, Deutschland
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Volker Mailänder
- Max-Planck-Institut für Polymerforschung, Mainz, Deutschland
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Christopher Blase
- Frankfurt University of Applied Sciences, Personalised Biomedical Engineering Lab, Frankfurt am Main, Deutschland
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Florian Ringel
- Universitätsmedizin Mainz, Neurochirurgische Klinik, Mainz, Deutschland
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Naureen Keric
- Universitätsmedizin Mainz, Neurochirurgische Klinik, Mainz, Deutschland
| Veröffentlicht: | 26. Juni 2020 |
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Gliederung
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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. We present a novel ovine model of osteoporotic bone to test a 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 vertebra 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 osteocalcin 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+-0.21%, while osteocalcin 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 showed improved pullout loads of CaP/P15 augmented screws compared to controls in decalcified bone. Difference of pullout loads between pre- and post-demineralizing process were also statistically significant (p < 0.001).
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.
