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OBJECTIVE: To determine if Pyk2-deficiency increases midpalatal suture bone mass and preserves sutural integrity after maxillary expansion. SETTING AND SAMPLE: Thirty-six male Pyk2 knockout (KO) and control (WT) mice at 6-weeks of age. MATERIALS AND METHODS: Mice received nickel-titanium spring expanders delivering 0g (no intervention control), 10g or 20g force for 14 days. High-resolution micro-CT was used to determine bone volume/tissue volume (BV/TV), sutural width and intermolar width. Effects on osteoclasts, chondrocytes and suture morphology were determined by histomorphometry. RESULTS: Pyk2-KO controls (0g) had 7% higher BV/TV compared with WT controls. Expanded Pyk2-KO maxillae also exhibited 12% (10g) and 18% (20g) higher BV/TV than WT mice. Although bone loss following expansion occurred in both genotypes, BV/TV was decreased to a greater extent in WT maxillae (−10% at 10g; −22% at 20g) compared with Pyk2-KO maxillae (−11% only at 20g) (p

Purpose Recent case reports suggest that amnion-chorion membranes (ACM) and dense polytetrafluoroethylene membranes (dPTFE) can be left exposed during ridge preservation. The aim of this study was to compare the effectiveness of these membranes in ridge preservation, particularly when they are intentionally left exposed. Materials and methods A split-mouth, single-blind, randomized trial design was used to compare treatments with the two membranes in 22 nonmolar sites on the same arch. Ridge dimensions were recorded clinically and with cone beam computed tomography prior to and 3 months after ridge preservation. Postoperative discomfort was recorded with Visual Analog Scale (VAS) forms. Mixed‑model analysis of variance was used to test significance. Results Clinical and radiographic ridge dimensions were not significantly different between the two treatments. ACM sites had significantly more osteoid and higher bone volume density but significantly less graft particles and bone surface density compared with dPTFE. Mineralized bone area and soft tissue area were not significantly different between the two treatments. ACM sites had significantly lower postoperative VAS scores compared with dPTFE. Conclusion Intentionally exposed ACM is equally effective in ridge preservation compared with dPTFE. Additionally, ACM use may aid in reducing postoperative VAS scores, and potentially result in better quality of bone available for implant placement, as evidenced by improved histomorphometric measures.

BACKGROUND Growth factors contained in platelet-rich plasma (PRP) have been reported to induce osteoblast differentiation in certain studies, while in others, osteogenesis has not been shown clinically. The aim of the present study was to verify the effect of PRP and its combination with rhBMP-2 as a controlled delivery system during sagittal suture distraction osteogenesis. METHODS Thirty-six-week male New Zealand white rabbits were randomly assigned to sagittal suture distraction osteogenesis groups treated with (1) PRP gel alone; and (2) PRP gel mixed with 10 μg rhBMP-2 (PRP/rhBMP-2), and a control group untreated. A heavy 200-g continuous mechanical force was applied for 33 days using a nickel titanium open spring to distract the suture between 2 miniscrew implants. The suture morphology was evaluated radiographically and histologically after sacrifice. RESULTS The amount of suture separation in the control group and the PRP gel group were statistically greater (P < 0.05) than in the PRP/rhBMP-2 gel group. Compared to the control group, the micro-CT and histologic analysis showed that the local application of PRP gel not only stimulates the new bone formation between the suture gap but accelerates the suture wound healing during distraction without suture fusion. There was a percent of total suture height 15.3 ± 9.5% fusion in PRP/rhBMP-2 gel group and the average thickness of cranium bone in the PRP/rhBMP-2 gel group was statistically greater (P < 0.05) than in the control group and the PRP gel group. CONCLUSIONS In this animal model, both PRP gel and PRP/rhBMP-2 gel are effective in improving new bone formation in suture distraction osteogenesis. PRP gel induces suture bone formation without suture fusion and accelerates the suture wound healing, while the PRP/rhBMP-2 gel group, in which the sutures fused prematurely, showed powerful bone formation ability aided by rhBMP-2. PRP can be alternatively use as a controlled release system for rhBMP-2, but caution should be used before proceeding with the application of high-dose growth factors around the growing craniofacial sutures.

Objective: BoneCeramic can regenerate bone in alveolar defects, but it remains unknown whether it is feasible to move a tooth through BoneCeramic grafting sites. The objective of this study was to investigate three-dimensional real-time bone responses and micromechanical properties in the grafting sites during orthodontic tooth movement. Methods: Sixty 5-week-old rats were randomly assigned into three groups to receive BoneCeramic, natural bovine cancellous bone particles (Bio-Oss), and no graft, respectively, after the extraction of the left maxillary first molar. After 4 weeks, the maxillary left second molar was moved into the extraction for 28 days. Dynamic bone microstructures and root resorption were evaluated using in vivo micro-computed tomography and histology. Stress distribution of tooth roots and biomechanical properties of corresponding bone tissue were examined by finite element methods and nanoindentation. Mixed-model analysis of variance was performed to compare the difference among time points with Bonferroni post hoc tests at the significance level of P < .05. Results: The BoneCeramic group had the least amount of tooth movement and root resorption volume and craters, highest bone volume fraction, trabecular number, mean trabecular thickness, microhardness, and elastic modulus, followed by Bio-Oss and the control group. The highest stress accumulated in the cervical region of the mesial roots. Conclusion: BoneCeramic has better osteoconductive potential and biomechanical properties and induces less root resorption compared with Bio-Oss grafting and naturally recovered extraction site.

Objective: To investigate three-dimensional microarchitecture and micromechanical properties of alveolar bone in the BoneCeramic grafting sites during orthodontic tooth movement. Materials and Methods: Sixty 5-week-old rats were randomly assigned into three groups to receive BoneCeramic, natural bovine cancellous bone particles (Bio-Oss), and no graft, respectively, after the extraction of the left maxillary first molar. After 4 weeks, the maxillary left second molar was moved into the extraction site for 28 days. Dynamic bone microstructures were evaluated using in vivo micro–computed tomography. Micromechanical properties and stress distribution of corresponding tissue were examined by nanoindentation and finite element methods. Mixed-model analysis of variance was performed to compare the difference among time points with Bonferroni post hoc tests at the significance level of P < .05. Results: The BoneCeramic group had the least amount of tooth movement and the highest bone volume fraction, tr...

Objective: To quantify the three-dimensional moments and forces produced by pretorqued nickel-titanium (NiTi) rectangular archwires fully engaged in 0.018- and 0.022-inch slots of central incisor and molar edgewise and prescription brackets. Materials and Methods: Ten identical acrylic dental models with retroclined maxillary incisors were fabricated for bonding with various bracket-wire combinations. Edgewise, Roth, and MBT brackets with 0.018- and 0.022-inch slots were bonded in a simulated 2 × 4 clinical scenario. The left central incisor and molar were sectioned and attached to load cells. Correspondingly sized straight and pretorqued NiTi archwires were ligated to the brackets using 0.010-inch ligatures. Each load cell simultaneously measured three force (Fx, Fy, Fz) and three moment (Mx, My, Mz) components. The faciolingual, mesiodistal, and inciso-occluso/apical axes of the teeth corresponded to the x, y, and z axes of the load cells, respectively. Each wire was removed and retested seven times. Three-way analysis of variance (ANOVA) examined the effects of wire type, wire size, and bracket type on the measured orthodontic load systems. Interactions among the three effects were examined and pair-wise comparisons between significant combinations were performed. Results: The force and moment components on each tooth were quantified according to their local coordinate axes. The three-way ANOVA interaction terms were significant for all force and moment measurements (P < .05), except for Fy (P > .05). Conclusion: The pretorqued wire generates a significantly larger incisor facial crown torquing moment in the MBT prescription compared to Roth, edgewise, and the straight NiTi wire.

Background/Objectives: This study investigated the biomechanical properties and bone-implant intersurface response of machined and laser surface-treated stainless steel (SS) mini-screw implants (MSIs). Material and Methods: Forty-eight 1.3mm in diameter and 6mm long SS MSIs were divided into two groups. The control (machined surface) group received no surface treatment; the laser-treated group received Nd-YAG laser surface treatment. Half in each group was used for examining surface roughness (Sa and Sq), surface texture, and facture resistance. The remaining MSIs were placed in the maxilla of six skeletally mature male beagle dogs in a randomized split-mouth design. A pair with the same surface treatment was placed on the same side and immediately loaded with 200g nickel–titanium coil springs for 8 weeks. After killing, the bone-implant contact (BIC) for each MSI was calculated using micro computed tomography. Analysis of variance model and two-sample t test were used for statistical analysis with a significance level of P

Introduction BoneCeramic (Straumann, Basel, Switzerland) can regenerate bone in alveolar defects after tooth extraction, but it is unknown whether it is feasible to move a tooth through BoneCeramic grafting sites. The objective of this study was to investigate 3-dimensional real-time root resorption and bone responses in grafted sites during orthodontic tooth movement. Methods Sixty 5-week-old rats were randomly assigned to 3 groups to receive BoneCeramic, natural bovine cancellous bone particles (Bio-Oss; Geistlich Pharma, Wolhusen, Switzerland), or no graft, after the extraction of the maxillary left first molar. After 4 weeks, the maxillary left second molar was moved into the extraction site for 28 days. Dynamic bone microstructures and root resorption were evaluated using in-vivo microcomputed tomography. Stress distribution and corresponding tissue responses were examined by the finite element method and histology. Mixed model analysis of variance was performed to compare the differences among time points with Bonferroni post-hoc tests at the significance level of P Results The BoneCeramic group had the least amount of tooth movement and root resorption volumes and craters, and the highest bone volume fraction, trabecular number, and mean trabecular thickness, followed by the Bio-Oss and the control groups. The highest stress accumulated in the cervical region of the mesial roots. Conclusions BoneCeramic has better osteoconductive potential and induces less root resorption compared with Bio-Oss grafting and naturally recovered extraction sites.

Introduction Midpalatal suture expansion could induce osteogenesis to correct maxillary insufficiency; cartilage formation could also be induced, and lower-magnitude forces might generate a preferable response pattern. In this study, we aimed for an enhanced understanding of the cartilage formatting effects of expansion. Methods Thirty 6-week-old male C57BL/6 mice were randomly and evenly assigned to 3 groups; the animals in each group received a sustained suture expansion at 0, 10, and 20 g, respectively. Ten additional mice were fed the same as the baseline controls and received no expansion. After 7 days, the animals were killed; coronal paraffin sections were stained using toluidine blue and safranin-O. The proliferating cell nucleus antigen, the nuclear antigen Ki-67, alkaline phosphatase, and matrix metalloproteinase 13 expressions were visualized with immunohistochemistry. All data were analyzed statistically, and the differences were considered significant at P Results Compared with the control, the cartilage matrix volume was significantly increased by the 20-g expansion, showing increased cartilage matrix and hypertrophic chondrocytes with the highest matrix metalloproteinase 13 expression. The 10-g expansion formed condensed proliferating chondrocyte masses, within which the highest percentages of proliferating cell nucleus antigen and Ki-67 positive cells were present. The 10-g and the 20-g expansions equally intensified the alkaline phosphatase expression. Conclusions The lower expansion (10 g) promoted chondrocyte proliferation and induced a more preferable suture cartilage response pattern compared with the higher expansion (20 g), which just increased the cartilage matrix production.

Background Epidermal growth factor receptor (EGFR) gene mutations identify patients with non-small cell lung cancer (NSCLC) who have a high likelihood of benefiting from treatment with anti-EGFR tyrosine kinase inhibitors. Sanger sequencing is widely used for mutation detection but can be technically challenging, resulting in longer turn-around-time, with limited sensitivity for low levels of mutations. This manuscript details the technical performance verification studies and external clinical reproducibility studies of the cobas EGFR Mutation Test, a rapid multiplex real-time PCR assay designed to detect 41 mutations in exons 18, 19, 20 and 21. Methods The assay’s limit of detection was determined using 25 formalin-fixed paraffin-embedded tissue (FFPET)-derived and plasmid DNA blends. Assay performance for a panel of 201 specimens was compared against Sanger sequencing with resolution of discordant specimens by quantitative massively parallel pyrosequencing (MPP). Internal and external reproducibility was assessed using specimens tested in duplicate by different operators, using different reagent lots, instruments and at different sites. The effects on the performance of the cobas EGFR test of endogenous substances and nine therapeutic drugs were evaluated in ten FFPET specimens. Other tests included an evaluation of the effects of necrosis, micro-organisms and homologous DNA sequences on assay performance, and the inclusivity of the assay for less frequent mutations. Results A >95% hit rate was obtained in blends with >5% mutant alleles, as determined by MPP analysis, at a total DNA input of 150 ng. The overall percent agreement between Sanger sequencing and the cobas test was 96.7% (negative percent agreement 97.5%; positive percent agreement 95.8%). Assay repeatability was 98% when tested with two operators, instruments, and reagent lots. In the external reproducibility study, the agreement was > 99% across all sites, all operators and all reagent lots for 11/12 tumors tested. Test performance was not compromised by endogenous substances, therapeutic drugs, necrosis up to 85%, and common micro-organisms. All of the assessed less common mutations except one (exon 19 deletion mutation 2236_2248 > AGAC) were detected at a similar DNA input level as that for the corresponding predominant mutation. Conclusion The cobas EGFR Mutation Test is a sensitive, accurate, rapid, and reproducible assay.

Objective: To observe the real-time microarchitecture changes of the alveolar bone and root resorption during orthodontic treatment. Materials and Methods: A 10 g force was delivered to move the maxillary left first molars mesially in twenty 10-week-old rats for 14 days. The first molar and adjacent alveolar bone were scanned using in vivo microcomputed tomography at the following time points: days 0, 3, 7, and 14. Microarchitecture parameters, including bone volume fraction, structure model index, trabecular thickness, trabecular number, and trabecular separation of alveolar bone, were measured on the compression and tension side. The total root volume was measured, and the resorption crater volume at each time point was calculated. Univariate repeated measures analysis of variance with Bonferroni corrections were performed to compare the differences in each parameter between time points with significance level at P < .05. Results: From day 3 to day 7, bone volume fraction, structure model index, trabecular thickness, and trabecular separation decreased significantly on the compression side, but the same parameters increased significantly on the tension side from day 7 to day 14. Root resorption volume of the mesial root increased significantly on day 7 of orthodontic loading. Conclusions: Real-time root and bone resorption during orthodontic movement can be observed in 3 dimensions using in vivo micro-CT. Alveolar bone resorption and root resorption were observed mostly in the apical third on day 7 on the compression side; bone formation was observed on day 14 on the tension side during orthodontic tooth movement.

Introduction Suture expansion stimulates bone growth to correct craniofacial deficiencies but has a high potential of treatment relapse. The objective of this study was to investigate whether there is a dose-dependent relationship between the recombinant human bone morphogenetic protein-2 (rhBMP-2) and bone formation during suture expansion. Methods Fifty 6-week-old male New Zealand white rabbits were randomly assigned to 5 groups to receive 0 (control), 0.01, 0.025, 0.1, or 0.4 mg/mL of rhBMP-2 delivered by absorbable collagen sponge placed over the interfrontal suture. The suture was expanded for 33 days by 200 g of constant force via a spring anchored with 2 miniscrew implants. Distance of suture expansion, suture volume, and cross-sectional area after expansion were measured using radiographs with bone markers and microcomputed tomography. Suture widths and mineralization appositional rates were calculated based on the widths between bone labels under an epifluorescent microscope. Software (Multilevel Win 2.0; University of Bristol, Bristol, United Kingdom) was used to model distance of suture expansion over time as polynomials to compare group differences. Wilcoxon signed rank tests were performed to compare the suture volume and cross-sectional area, mineral apposition rate, and suture width between groups. The significance level was set at P = 0.05. Results Whereas the sutures were expanded in all groups, sutures were expanded by significantly greater amounts in the control and the 0.01 mg/mL groups without fusing the sutures than in the 0.025, 0.1, and 0.4 mg/mL groups with fusing sutures. Compared with the controls, the 0.01 mg/mL group showed significantly lower suture volumes, cross-sectional areas, and suture widths after expansion. The mineral apposition rate was significantly higher in the 0.01 mg/mL group than in the controls from days 10 to 30. Conclusions The 0.01 mg/mL dose of rhBMP-2 delivered by absorbable collagen sponge can stimulate bone formation at the bony edges of the suture during suture expansion; however, higher concentrations cause suture fusion. With an appropriate concentration, rhBMP-2 might facilitate suture expansion for clinical uses.

Suture compression is a widely used approach to inhibit maxillary growth; however, biological responses in sutures to compressive force are still unclear. The objective of this pilot study was to investigate the matrix metalloproteinase (MMP) expression and osteoclast activities during the midpalatal suture compression.56 six-week old male C57BL/6 mice were randomly assigned to the control and compression groups. The mice in the compression and control groups received helix springs bonded to the maxillary molars delivering initial compressive forces of 0.20 and 0N (no activation), respectively. On Days 1, 4, 7 and 14, animals were sacrificed and scanned using micro-computed tomography to quantify suture width and bone mineral density. Serial histological sections were stained with HE, TRAP, and immunohistochemistry to observe changes in bone resorption, osteoclast activities, and MMP-1, 8, and 13 expressions. Bone volume/total volume (Bv/Tv) ratio, osteoclast count, osteoclast covering area, and MMP expression intensity were measured. The Mann-Whitney and the Kruskal-Wallis tests with Bonferroni post-hoc corrections were performed to compare differences between groups and between time points in the same group at significant level of P0.05.Compared to the control, suture width in the compression group was significantly reduced on Day 1, but continuously widened with reduced bone mineral density afterwards. With MMP-1 and -13 evidently intensified expressions, osteoclast number and activities significantly increased, leading to reduced Bv/Tv ratio and progressive bone resorption from Days 4 to 14.Suture compression elevated the MMP-1 and 13 expressions, activated osteoclasts, reduced bone density, and induced bone resorption adjacent to the suture. It suggests that suture compression can be used for bone volume reduction.

While both intermittent and continuous forces are commonly used to expand sutures, it remains unclear which force is most effective. Using nickel-titanium (NiTi) open coil springs (50 g) and 3 mm long miniscrew implants (MSIs) for skeletal anchorage, intermittent and continuous forces were used to expand the midsagittal sutures in 18 New Zealand white juvenile male rabbits, 11 weeks of age, for 29 days. In the intermittent group, expansion forces of 50 g were delivered for 5 days (on) and paused for 1 day (off); the on/off cycles were repeated five times. Expansion forces of 50 g were delivered for 29 consecutive days in the continuous group. Longitudinal biometric and histomorphometric analyses were performed to evaluate sutural separation and bone formation using implanted tantalum bone markers and fluorescent bone labelling, respectively. Multilevel modelling procedures were undertaken to compare the groups and time intervals. Continuous forces produced significantly greater overall sutural separation (1.3 mm) than intermittent forces (0.8 mm). Although they were delivered over a period of time 86 per cent as long, intermittent forces produced only 61 per cent of the sutural separation of continuous forces. Between days 7 and 17, continuous forces resulted in significantly greater mineral apposition and bone formation rates than intermittent forces. Intermittent forces produced approximately 59 per cent as much mineral apposition and 61 per cent as much bone formation as continuous forces. Due to greater sutural separation and bone formation, continuous forces provide a more effective approach for separating sutures than intermittent forces.

Background The occurrence of mandibular defects caused by tumors has been continuously increasing in China in recent years. Conversely, results of the repair of mandibular defects affect the recovery of oral function and patient appearance, and the requirements for accuracy and high surgical quality must be more stringent. Digital techniques — including model reconstruction based on medical images, computer-aided design, and additive manufacturing — have been widely used in modern medicine to improve the accuracy and quality of diagnosis and surgery. However, some special software platforms and services from international companies are not always available for most of researchers and surgeons because they are expensive and time-consuming. Methods Here, a new technical solution for guided surgery for the repair of mandibular defects is proposed, based on general popular tools in medical image processing, 3D (3 dimension) model reconstruction, digital design, and fabrication via 3D printing. First, CT (computerized tomography) images are processed to reconstruct the 3D model of the mandible and fibular bone. The defect area is then replaced by healthy contralateral bone to create the repair model. With the repair model as reference, the graft shape and cutline are designed on fibular bone, as is the guide for cutting and shaping. The physical model, fabricated via 3D printing, including surgical guide, the original model, and the repair model, can be used to preform a titanium locking plate, as well as to design and verify the surgical plan and guide. In clinics, surgeons can operate with the help of the surgical guide and preformed plate to realize the predesigned surgical plan. Results With sufficient communication between engineers and surgeons, an optimal surgical plan can be designed via some common software platforms but needs to be translated to the clinic. Based on customized models and tools, including three surgical guides, preformed titanium plate for fixation, and physical models of the mandible, grafts for defect repair can be cut from fibular bone, shaped with high accuracy during surgery, and fixed with a well-fitting preformed locking plate, so that the predesigned plan can be performed in the clinic and the oral function and appearance of the patient are recovered. This method requires 20% less operating time compared with conventional surgery, and the advantages in cost and convenience are significant compared with those of existing commercial services in China. Conclusions This comparison between two groups of cases illustrates that, with the proposed method, the accuracy of mandibular defect repair surgery is increased significantly and is less time-consuming, and patients are satisfied with both the recovery of oral function and their appearance. Until now, more than 15 cases have been treated with the proposed methods, so their feasibility and validity have been verified.

Introduction The goal of this study was to evaluate whether human recombinant bone morphogenetic protein-2 (rhBMP-2) enhances sutural bone formation or causes premature sutural fusion. Methods Thirty 6-week-old rabbits underwent midsagittal sutural expansion. The animals were randomly assigned to receive 0 (control), 0.1 mg per milliliter, or 0.4 mg per milliliter of rhBMP-2, delivered by an absorbable collagen sponge placed over the suture. A 100-g constant force was delivered for 33 days by using a nickel-titanium spring to expand the suture between 2 miniscrew implants anchored in the frontal bone. At days 10, 20, and 30, sutural separation was evaluated and modeled over time as polynomials by using multilevel statistical procedures. Bone formation and sutural gaps were analyzed histomorphometrically between days 10 and 20 and days 20 and 30. Results The control group showed significantly greater overall sutural bone formation than did the 2 rhBMP-2 groups. Over time, bone formation decreased significantly in all groups. Between days 10 and 20, the 0.4 mg per milliliter group produced significantly more (58%) bone than did the 0.1 mg per milliliter group; there were no significant differences in bone formation between the 2 experimental groups between days 20 and 30. Both 0.1 and 0.4 mg per milliliter of rhBMP-2 in the absorbable collagen sponge caused premature fusion by forming a bony bridge connecting the ectocranial aspect of the sutural margins. Premature fusion significantly reduced sutural separation between 10 and 30 days (to 56% and 62% of control values for the 0.1 and 0.4 mg per milliliter groups, respectively). There were no significant differences in sutural separation between the 0.1 and 0.4 mg per milliliter groups. Conclusions Compared with the 0.1 mg per milliliter group, 0.4 mg per milliliter of rhBMP-2 accelerated sutural bone formation between days 10 and 20. After 10 to 20 days, rhBMP-2 in the absorbable collagen sponge caused premature sutural fusion, despite the constant expansion forces.