by Sándor Farkasdi (Hungary), Matthieau Renaud, Gergely Hriczó-Koperdak, Bence Szabó, Csaba Dobó-Nagy, Wu Gang, Frederic Cuisinier, Gábor Varga

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Objectives: Functional tooth replacement and bone regeneration are a routine part of daily practice in modern dentistry, but there is no reproducible and relatively inexpensive animal model for multiple testing. We aimed to develop a new model for evaluating bone regeneration, osseointegration and critical size defects. Methods: We used a special guided approach at the level of the C4–C5 vertebrae in Wistar rats after cutting the tail for parallel placement of customised titanium implants. Bone remodelling around the implants was evaluated after 4–16 weeks. Biomechanical properties were characterised by measuring the maximum extraction force and using micro-CT, histomorphometry and resonance frequency analysis. Critical size defects for bone tissue engineering and implant placements for titanium body experiments were evoked by drilling each of the first four caudal vertebrae from the side, thus allowing multiple comparisons, and micro-CT and histology were used to evaluate bone growth. Results: The percentage regeneration was only of 20% ± 5% when bone grafting particles alone were used to fill defects. Bio-Oss[tm] was used for positive controls but the material was radio-opaque and could not be assessed by micro-CT. Histology revealed collagen network formation in defects filled with bone grafting material, but not in those with Bio-Oss[tm]. Immunohistochemical assays confirmed the presence of bone markers such as osteocalcin and type I collagen, and the presence of bone cells of both human and rat origin. A positive correlation was found between measurements made using various in vivo techniques(r=0.8498). Statistically significant increases were found during evaluations at 4, 8, 12 and 16 weeks in terms of strength of osseointegration. Histomorphometry and micro-CT showed new bone formation on the implant surfaces, suggesting the direct connection occurring between bone and titanium. Conclusion: These results support the use of the caudal vertebrae bone regeneration rat model as a useful standard for preclinical evaluation of tissue engineering and osseointegration.
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