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1.
  • Oliveira, G, et al. (author)
  • Effect of systemic administration of cyclosporine on the repair of critical size calvaria defects in rats
  • 2014
  • In: Clinical Oral Implants Research. - : John Wiley & Sons. - 0905-7161 .- 1600-0501. ; 25:s10, s. 289-289
  • Journal article (other academic/artistic)abstract
    • Background: To facilitate healing, bone defects are often grafted with bone substitute materials, for example of xenogenic origin or laboratory made alloplasts. An essential process for healing in bone defects is remodeling; thus, long-term use of specific drugs that interfere with bone remodeling may compromise healing of bone defects despite the use of substitute materials. Cyclosporine is an immunosuppressive drug used for the treatment of autoimmune disorders and in the prevention of organ rejection in transplant patients. Pre-clinical studies have shown that use of cyclosporine reduces bone density and also impairs healing of vascularized allografts and dental implant osseointegration. There is limited information on the effect of cyclosporine use on the healing of bone defects grafted with substitute materials. Aim/Hypothesis: To evaluate by means of micro-CT the effect of systemic administration of cyclosporine on the healing of critical- size calvaria defects in rats, grafted with deproteinized bovine bone or biphasic calcium phosphate. Material & Methods: Sixty rats were divided in two equal-sized groups. Animals in one group received systemic administration (per os) of Cyclosporine Csa (10 mg/kg/day) and those in the other group received sterile saline. After 15 days, a cylindrical critical- size defect (5 mm in Ø) was created in the calvaria of the rats. The defects were grafted with a standardized quantity of deproteinized bovine bone (BO group) or biphasic calcium phosphate (b-tricalcium phosphate 40%/hydroxyapatite 60%) (BC group) or were left empty for spontaneous healing (E group), i.e. 10 animals per treatment combination. Use of Cyclosporine or saline was continued for 15 and 60 days post-operative, where five animals per treatment combination were euthanized. Blocks of specimens containing the defect and surrounding tissues were scanned with micro-CT, operated at 50 kV and 800 mA and with image pixel set of 17.48 lm. Transaxial sections – each 35 lm thick – were generated throughout the dataset and 40 equidistant sections comprising the entire defect volume were selected for analysis. A circular region of interest (5 mm in Ø) was superimposed on the defect and the relative quantities of tissues within each defect was estimated semi-automatically by dedicated software using a gray-scale threshold between 55 and 250 to evaluate the percentage of mineralized tissues (new bone and biomaterial; MT), and a threshold of 55 and 90 to evaluate the percentage of bone. Non-paired t-tests and one-way ANOVA/Tukey tests were used to evaluate differences (P < 0.05). Results: Cyclosporine treated animals showed significantly less bone in E defects comparing to animals receiving saline at both experimental periods (15 days: 11.3 3.3 vs. 28.0 3.9; 60 days: 7.6 2.22 vs. 34.8 9.0). Cyclosporine treated animals showed also significantly less MT compering to saline controls in BC grafted defects at 15 days of healing (36.6 6.7 vs. 53. 10.1), but not after 60 after days (46.3 11.1 vs. 42.7 10.6). In BO grafted defects, systemic administration of cyclosporine resulted in reduced amounts of MT comparing to saline controls at 15 days (51.9 9.4 vs. 65.9 14.1; P > 0.05), but not after 60 days of healing (61.7 6.9 vs. 65.2 12.8). At 15 days of healing, the amount of residual bone substitute was significantly less in the cyclosporine group comparing to that observed in the saline group (BO: 32.5 11.5 vs. 50.9 13.8; BC: 17.2 4.5 vs. 32.2 12.2). Conclusion & Clinical implications: Systemic administration of cyclosporine impaired bone healing in critical-size calvaria defects in rats during the early healing period. In addition, systemic administration of cyclosporine accelerated resorption of bone substitute materials during the early healing period.
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2.
  • Oliveira, G, et al. (author)
  • Evaluation of ASU Administration on Bone Healing in Calvarial Defects
  • 2014
  • Conference paper (other academic/artistic)abstract
    • Objective: Avocado/soybean unsaponifiables (ASU) is indicated as supplement for the palliative treatment of rheumatoid arthritis and osteoarthritis. In vitro studies have shown that ASU enhances Transforming Grown Factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) expression. The objective of this study was to evaluate the influence of ASU (Piascledine 300, Expanscience Lab, France) on bone healing in critical-size calvarial defects (CCD) in the presence and absence of bone substitutes. Method: A full thickness CCD defect (Ø 5mm) was made in each of 84 male wistar rats. The defects were implanted with either deproteinized bovine bone (DBB) (Bio-Oss, Geistlich Pharma, Switzerland) or a biphasic tricalcium phosphate/hydroxyapatite (TCP/HA) (Straumann Bone Ceramic, Straumann, Switzerland) particulate material, or filled only with coagulum (COA). Starting 15 days prior to surgery, ASU (0.6 gr. per Kg body weight) or saline (CTR) was administered daily by gavage until sacrifice 15 or 60 days post-op (7 animals per group at each observation period). Tissue composition within the defect was estimated by histomorphometry. Non-paired T- test, one-way Anova, and Tukey´s tests were used to evaluate differences (P < 0.05). Result: Bone fill in the COA-ASU group was significantly higher comparing to that in the COA-CTR group, both at 15- (46.4±10.4 vs. 29.0±8.8) and 60 days (52.1±6.1 vs. 42.7±5.2). No significant differences in bone fill were observed between DBB-ASU and DBB-CTR at day 15 (29.3±4.5 vs. 31.4±7.5) and day 60 (33.1±4.6 vs. 39.9±10.5), as well as between TCP/HA-ASU and TCP/HA-CTR at day 15 (33.3±6.7 vs. 33.0±6.5) and day 60 (31.7±5.0 vs. 39.6±8.7). Bone fill in COA-ASU group was significantly more than in DDB-ASU and TCP/HA-ASU groups at day 60. Conclusion: ASU enhanced bone healing in CCD originally filled only with coagulum, while implantation of DDB and TCP/HA appeared to obstruct the positive effect of ASU.
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3.
  • Oliveira, G. J. P. L., et al. (author)
  • Effect of avocado/soybean unsaponifiables on ligature-induced bone loss and bone repair after ligature removal in rats
  • 2016
  • In: Journal of Periodontal Research. - : Wiley-Blackwell Publishing Inc.. - 0022-3484 .- 1600-0765. ; 51:3, s. 332-341
  • Journal article (peer-reviewed)abstract
    • Background and ObjectiveThe aim of this study was to evaluate the effects of administration of avocado/soybean unsaponifiable (ASU), a drug that is commonly used in the treatment of rheumatoid arthritis, on ligature-induced bone loss and bone repair after ligature removal in rats. Material and MethodsEighty-four rats were randomly assigned to four groups of equal size and received a daily gavageof either sterile saline [control (CTR)] or ASU (0.6mg/kg), starting 7d before (ASU/-7), on the day of (ASU/0) or 7d after (ASU/+7) periodontitis induction. Periodontitis was induced by placing silk ligatures into the gingival sulcus of the second maxillary molars for 7d; after 7d, the ligatures were removed. Seven rats from each group were sacrificed, 7, 15 or 30d after ligature removal. Bone resorption was evaluated by histomorphometry and micro-computed tomography (micro-CT). Immunohistochemistry was used to evaluate the expression of TRAP, RANKL and alkaline phosphatase (ALP), and quantitative PCR (qPCR) was used to evaluate the levels of interleukin-1beta (Il1), tumor necrosis factor alpha (Tnf), interleukin-6 (Il-6), Rankl and Alp. Statistical analysis was performed using the Shapiro-Wilk test, ANOVA and Tukey's test for normal data, and using the Kruskall-Wallis and Dunnet's tests for non-normal data (p<0.05 ResultsHistomorphometry and micro-CT analysis showed greater bone resorption in the CTR group than in the ASU/0 (15d) and ASU/+7 (7 and 15d) groups. The CTR group also presented with a higher expression of TRAP (15 and 30d) and RANKL (7 and 15d) compared with ASU/0 and ASU/+7 groups. Similarly, qPCR analysis showed higher levels of Rankl and Il1 mRNAs, and lower levels of Alp mRNA, in the CTR group compared with all other groups (for all periods ConclusionASU exhibited a positive effect on bone repair following ligature-induced periodontitis in rats
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5.
  • Aludden, H., et al. (author)
  • Radiographic changes in height and volume after lateral GBR procedures with different ratios of deproteinized bovine bone mineral and autogenous bone at different time points. An experimental study
  • 2021
  • In: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 32:2, s. 167-179
  • Journal article (peer-reviewed)abstract
    • Objective Estimate changes in augmentation height and volume after lateral guided bone regeneration (GBR) augmentation with different ratios of deproteinized bovine bone mineral (DBBM) and particulate autogenous bone (PAB) and autogenous bone block (ABB), at different time points. Material and methods Twenty-four minipigs were randomly allocated into three healing periods. Lateral augmentation in 96 sites with standardized quantity of graft material was performed with different ratios of DBBM and PAB (50:50, 75:25, and 100:0) and ABB in combination with DBBM, covered by a collagen membrane. Changes in augmentation height and volume were assessed on CT volumes acquired 10, 20, and 30 weeks after surgery. Results Reduction in bone augmentation height was as follows: 50:50-1.7 mm (-33.1%), 75:25-1.8 mm (-37.8%), 100:0-1.7 mm (-35.8%), and ABB - 0.2 mm (-3.7%), after 30 weeks. The augmentation height was significantly better preserved with ABB compared to 50:50, 75:25, and 100:0, while no significant difference was present among particulate grafts. No significant difference in volumetric reduction was found among 50:50, 75:25, 100:0 and ABB after 30 weeks, while 100:0 presented significant less reduction compared to 50:50, 75:25 and ABB after 10 and 20 weeks. Conclusions Augmentation height following GBR was better preserved with ABB covered with DBBM. Addition of PAB to DBBM did not affect the changes in height of the graft. The volumetric stability seems to be comparable for ABB covered by DBBM and all particulate grafts after 30 weeks. However, DBBM alone revealed significant less volume reduction in the early healing phase.
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