Effect of rhBMP-2 applied with a 3D-printed titanium implant on new bone formation in rabbit calvarium
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Abstract:
Objective This study sought to compare the biocompatibility of a three-dimensional (3D)-printed titanium implant with a conventional machined titanium product, as well as the effect of such implant applied with recombinant human Bone Morphogenetic Protein Type 2 (rhBMP-2) for guided bone regeneration. Methodology Disk-shaped titanium specimens fabricated either by the conventional machining technique or by the 3D-printing technique were compared by MC3T3-E1 cells cytotoxicity assay. New bone formation was evaluated using a rapid prototype titanium cap applied to the calvaria of 10 rabbits, which were divided into two groups: one including an atelopeptide collagen plug on one side of the cap (group I) and the other including a plug with rhBMP-2 on the other side (group II). At six and 12 weeks after euthanasia, rabbits calvaria underwent morphometric analysis through radiological and histological examination. Results Through the cytotoxicity assay, we identified a significantly higher number of MC3T3-E1 cells in the 3D-printed specimen when compared to the machined specimen after 48 hours of culture. Moreover, morphometric analysis indicated significantly greater bone formation at week 12 on the side where rhBMP-2 was applied when evaluating the upper portion immediately below the cap. Conclusion The results suggest that 3D-printed titanium implant applied with rhBMP-2 enables new bone formation.Keywords:
Calvaria
Biocompatibility
Bone Formation
Calvaria
Bone Formation
Densitometry
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Purpose To evaluate the local effect of simvastatin (SVT) combined with deproteinized bovine bone (DBB) with hydroxyapatite/β-tricalcium phosphate biphasic ceramics (HA/TCP) and with collagen sponge (CS) on bone repair in critical size defects (CSDs) in rat calvaria. Methods Forty-two 5-mm diameter CSDs were made bilaterally in the calvaria of 18 rats. The animals were allocated according to the type of biomaterial and associations used to fill the CSD. After 8 weeks, the animals were euthanized, and their calvaria were evaluated for repaired tissue composition using histologic and histometric analyses. Results In the histometric analysis, the use of SVT showed to increase bone formation in the CSDs when combined with all the bone substitutes tested in this study (p<0.05). Greater bone formation was observed in the groups with SVT compared to the groups without SVT. Conclusions The use of SVT without the need for a vehicle and combined with a commercially available biomaterial may be a cheaper way to potentiate the formation of bone tissue without the need to produce new biomaterials. Therefore, SVT combined with DBB induced significantly greater new bone formation than did the other treatments.
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In this study, hydroxypropyl methylcellulose (HPMC) was mixed with particle-type xenografts, derived from two different species (bovine and porcine), to increase the manipulability of bone grafts and compare the bone regeneration ability. Four circular defects with a diameter of 6 mm were formed on each rabbit calvaria, and the defects were randomly divided into three groups: no treatment (control group), HPMC-mixed bovine xenograft (Bo-Hy group), and HPMC-mixed porcine xenograft (Po-Hy group). At eight weeks, micro-computed tomography (µCT) scanning and histomorphometric analyses were performed to evaluate new bone formation within the defects. The results revealed that the defects treated with the Bo-Hy and the Po-Hy showed higher bone regeneration than the control group (p < 0.05), while there was no significant difference between the two xenograft groups (p > 0.05). Within the limitations of the present study, there was no difference in new bone formation between porcine and bovine xenografts with HPMC, and bone graft material was easily moldable with the desired shape during surgery. Therefore, the moldable porcine-derived xenograft with HPMC used in this study could be a promising substitute for the currently used bone grafts as it exhibits good bone regeneration ability for bony defects.
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Bone Formation
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Objective: To study the effect of BAG on bone induced by recombinant human bone morphogenetic protein-2 and to evaluate the bone regenerative potential of rhBMP-2 on adult domestic rabbits calvarial bone. Methods: 16 adult rabbits were devided into 4 groups. Tight subperiosteal pockets were created on adult rabbit calvarial bone and implanted with various grafts: rhBMP-2/BAG, BAG, rhBMP-2 and no implant as control group. Evaluations consist clinical examinations, histology and histomorphometry. Results: rhBMP-2 /BAG induced bone formation by mean of intramembranous bone tormation. The new bone combined directly to host bone. At the 2,4 and 8 weeks post-operation, the width of new bone formated in group rhBMP-2/BAG was significantly larger than group BAG (P0.05), and the bone tomation in group BAG was larger than the rest two groups. Conclusions: BAG has good conductibility and absorbability. rhBMP-2/BAG can promote bone angmentation in calvaria and is a promising bone substitute in clinical applications.
Calvaria
Bone Formation
Intramembranous ossification
Human bone
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The clinical therapeutic application of experimental strategies requires extensive preclinical experimentation in appropriate animal models. Thus, a valid model must be established. The aim of the present study was to determine the critical size defect (CSD) of rat calvaria that is unable to undergo spontaneous bone regeneration. Forty Sprague Dawley female rats (body weight (bw): 250 +/- 20 g) were distributed in two groups. Circular surgical defects, 3 mm (Group A) and 5 mm (Group B) in diameter, were produced in the parietal bones. The animals were left untreated and sacrificed 1, 2, 3 and 6 weeks after surgery. Group A showed bone formation at the experimental site, increasing from 1 week (4.5%) to 6 weeks (46%). However, Group B showed scarce bone formation (less than 10%) throughout the experimental period. We may conclude that a defect 5 mm in diameter is a critical size defect (CSD) because it is the minimum bone defect size that requires treatment to heal. Thus, a circular defect 5 mm in diameter in rat calvaria would be an appropriate experimental model to study bone therapies.
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Parietal bone
Bone Formation
Rat model
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It has been stated that the bone allografts from different tissue banks may lead to various amount of bone induction, so the aim of this study was to evaluate bone regeneration of three demineralized allografts both histologically and histomorphometrically in rabbits calvaria bone defects.In this double-blind randomized experimental animal study, 32 critical size defects (11-mm diameter) in the calvaria of 16 male New Zealand white rabbits were randomly filled with three demineralized freeze-dried bone allografts (DBM, CENOBONE, DEMBONE), while the nongrafted defect was regarded as control group. After 6 and 12 weeks of healing, the experimental animals were euthanized for specimen preparation. After histological evaluation, histomorphometric analysis was performed to quantify new bone formation and remained graft particles. The data were analyzed by one-way ANOVA with Tukey's ad-hoc test and t-test. (P < 0.05 was considered to be statistically significant).Mean percentage of bone formation increased between two healing time, but it was not statistically significant in all groups except DBM which the bone formation significantly decreased (P = 0.04). There were not statistically significant differences between three allografts in remained particles and bone formation in both healing times and they could not induce significantly more bone formation than control group.Both test and control groups resulted in successful new bone formation. No difference was noted in bone formation and remained particles between three commercial bone allografts. Further studies in this issue may be needed.
Calvaria
Bone Formation
Histology
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Synthetic octacalcium phosphate (OCP) has been shown to enhance bone formation and to biodegrade if implanted into bone defects. Here, we hypothesized that an OCP-atelocollagen complex (OCP/Col) is biodegradable and can induce bone formation in a thickness-dependent manner when implanted into the calvaria. OCP/Col disks (diameter, 9 mm; thickness, 1 or 3 mm) were implanted into a subperiosteal pocket in the calvaria of 12-week-old Wistar rats for 4, 8, and 12 weeks and subsequent bone formation was monitored. X-ray diffraction analysis and Fourier transform infrared spectroscopy showed that OCP in the OCP/Col implants was converted into a carbonate-rich apatite after 4 weeks. Although thinner disks tended to be replaced by new bone, thicker disks were progressively resorbed by osteoclast-like cells until 12 weeks, possibly via the increased mechanical load in the subperiosteal pocket. Therefore, OCP/Col can increase appositional intra-membranous bone formation if the appropriate size of the implant is applied.
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Octacalcium phosphate
Bone Formation
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