Application of metal artifact reduction algorithm for CBCT diagnosis of temporary anchorage device-tooth root contact: inadequate to reduce false-positive rate.

OBJECTIVES: It was recently found that when cone beam computed tomography (CBCT) was used to examine temporary anchorage device (TAD)-tooth root contact, it tends to yield high false-positive (FP) diagnoses. This study investigated whether application of a metal artifact reduction (MAR) algorithm or reducing CBCT scan voxel-size can remediate this problem. METHODS: 18 fresh pig cadaver mandibles underwent TAD placement bilaterally at first molar lingual furcation regions. CBCT scans were taken under varied MAR (absence, presence) and voxel-size (400 µm, 200 µm) settings. Then, TADs were removed and a micro-CT scan (27 µm voxel-size) of the TAD placement site was performed. Three raters, blinded of CBCT scan setting, independently diagnosed whether TADs were in contact with roots. The reliability and accuracy of CBCT diagnoses using micro-CT as the gold-standard were statistically examined. RESULTS: Generally, CBCT diagnoses had intrarater (Cohen's κ: 0.54-1) and interrater (Fleiss' κ: 0.73-0.81) reliability, within the moderate to excellent range, which did not vary with MAR setting or scan voxel-size. For diagnostic accuracy, FP rate among all raters was mostly in the 15-25% range and did not change with MAR or scan voxel-size settings (McNemar tests, p > 0.05) while false-negative rate was relatively minimal and only occurred to one rater (9%). CONCLUSIONS: When using CBCT to diagnose possible TAD-root contact, applying a currently available Planmeca MAR algorithm or reducing CBCT scan voxel-size from 400 µm to 200 µm may not decrease FP rate. Further optimization of the MAR algorithm for this purpose may be needed.

Effects of porcine bone marrow-derived platelet-rich plasma on bone marrow-derived mesenchymal stem cells and endothelial progenitor cells.

This study investigated the abundance of pro-regenerative growth factors in bone marrow-derived platelet-rich plasma (BM-PRP) and their effects on bone marrow-derived mesenchymal stem cells (BM-MSC) and bone marrow-derived endothelial progenitor cells (BM-EPC). Four 4-5 months-old domestic pigs were included, and each underwent bone marrow aspiration from its humerus bones and processed into bone marrow aspiration concentrate (BMAC) samples. The plasma and cellular portions of BMAC were subsequently separated and collected. The concentration of growth factors including BMP-2, PDGF-BB, TGF-ß1 and VEGF in the plasma portion was measured and compared between BM-PRP and bone marrow-derived platelet-poor plasma (BM-PPP). It was found that platelet count was significantly higher in BM-PRP than in BM-PPP, but the concentration of above-mentioned growth factors was not significantly different between BM-PRP and BM-PPP. As most existing literature has indicated the regenerative potency of PRP, this study focused on assessing the effect of BM-PRP treatment on BM-MSC and BM-EPC proliferation, osteogenic differentiation and angiogenesis capacity by comparing samples with 2.5% BM-PRP treatment and samples without BM-PRP treatment (control). In response to BM-PRP treatment, the cellular doubling time increased with culturing time and was significantly shorter in the BM-PRP-treated samples than in control samples. For osteogenic differentiation, BM-PRP-treated BM-MSCs demonstrated a time-dependent increase in alkaline phosphatase (ALP) activity and expression levels of osteogenic differentiation markers. For the expression of angiogenic genes, none of the differences reached statistical significance despite a tendency of stronger expression at day 18 in BM-PRP-treated BM-EPCs. In conclusion, this in vitro study suggests that most BMP-2, PDGF-BB, TGF-ß1 and VEGF-A contained in BM-PRP are not platelet-released and BM-PRP may have some stimulation (less than 1-fold) for MSC, EPC proliferation and MSC osteogenic differentiation.

Reliability and accuracy of assessing temporary anchorage device-tooth root contact with cone-beam computed tomography.

INTRODUCTION: This study was aimed at investigating the reliability and accuracy of cone-beam computed tomography (CBCT) diagnosis of contact between a temporary anchorage device (TAD) and tooth root and assessing any effect produced by metal brackets, imaging software program, and image segmentation or color enhancement tools. METHODS: Eighteen fresh pig mandibles were used. TADs (Vector, 1.4 × 8 mm) were placed at the buccal intermolar alveolar bone on both sides of the mandibles. With soft tissue kept intact, each mandible underwent CBCT scans (voxel size, 400 µm) before and after placing TADs, and after placing metal brackets on involved molars. Alveolar bone specimens containing the TADs were then exposed to microcomputed tomography (microCT) scans (voxel size, 27 µm) after TAD removal. Two independent raters, blinded of image identity, diagnosed TAD-root contact using ImageJ (National Institutes of Health and the Laboratory for Optical and Computational Instrumentation, University of Wisconsin, Madison, Wis) for microCT; Dolphin (Dolphin Imaging and Management Solutions, Chatsworth, Calif) and Anatomage software programs (Anatomage, Santa Clara, Calif) for CBCT images. Intrarater and interrater reliability and diagnostic accuracy were statistically assessed using Cohen kappa and McNemar tests. RESULTS: Intrarater and interrater reliability of TAD-root contact diagnoses were perfect for microCT diagnoses (κ = 1), generally moderate to good (κ >0.5) for CBCT diagnoses except for the use of color enhancement tools (κ <0.25). For diagnostic accuracy, there was generally a low agreement (κ <0.45) between CBCT and microCT (gold standard). The percent accuracy ranged from 68.1% to 79.2% and was not different among raters, bracket presence/absence, or software choices (chi-square tests, P >0.05). Overall, diagnostic sensitivity was above 80%, whereas specificity was below 55%. CONCLUSIONS: Despite good reliability, diagnoses of TAD-root contact using 400 µm voxel size CBCT imaging tend to be inaccurate, with a likelihood of high false-positive diagnoses.

Enhancement of bone marrow aspirate concentrate with local self-healing corticotomies.

Bone marrow aspirate concentrate (BMAC) is a potentially useful biological product for bone regeneration. This study investigated whether BMAC can be enriched by local minor corticotomies. Five 4-month-old domestic pigs were used with each pig undergoing two minor corticotomies at one randomly-selected tibia. Two weeks after the operation, bone marrow was aspirated from both tibiae and processed into BMAC samples. The amount of mesenchymal stem cells (MSCs) and the concentration of several regenerative growth factors contained in BMAC, as well as the proliferative and osteogenic differentiation capacity of MSCs, were compared between the corticotomy and the control sides. Another four weeks later, healing of the corticotomies was evaluated by radiographic and histological methods. The results demonstrated that BMAC from the corticotomy side contained significantly more MSCs than the control side. MSCs from the corticotomy side also proliferated significantly faster and tended to have stronger osteogenic differentiation than those from the control side. In contrast, the protein concentration of TGF-ß, BMP-2 and PDGF contained in BMAC was only minimally changed by the corticotomies. The corticotomies in all pigs healed uneventfully, showing complete obliteration of the corticotomy gaps on CT images. Comparison between the two sides showed that the corticotomy side had thicker and denser cortical bone and more abundant osteogenic cell differentiation than the control side. These findings suggest that the quantity and proliferative/osteogenic differentiation capacity of MSCs contained in local BMAC can be enhanced by minor corticotomies, and spontaneous healing of the corticotomy can be completed within 6 weeks of the operation.

Xenogeneic mesenchymal stem cell transplantation for mandibular defect regeneration.

BACKGROUND: It is commonly accepted that xenogeneic stem cell transplantation for tissue engineering is faced with host immune rejection. Using a rat critical-size mandibular defect model, this study examined whether the immune rejection can be evaded by diminishing T-cell immunity. METHODS: To examine donor cell survival and host immune reaction, pig bone marrow-derived mesenchymal stem cells (BM-MSCs) were labeled with CM-DiI, loaded onto gelatin sponge (5 × 106 cells/scaffold), and transplanted into 5-mm mandibular defects of immunocompetent and T cell-deficient athymic rats. To examine the effects of xenogeneic BM-MSCs on bone regeneration, athymic rats undergone the same surgeries were terminated at post-operative weeks 1, 3, and 6. Control rats underwent the same jaw surgery without BM-MSC transplantation. RESULTS: The density of CM-DiI-labeled BM-MSCs decreased with time in both strains of rats. Although it was substantially higher in athymic rats than in immunocompetent rats at post-operative day 1, by day 3-7 the density became comparable between the two strains of rats. Apoptosis reflected by cleaved Caspase-3 staining was low in both strains. Stronger infiltration of neutrophils, macrophages, B cells and CD8+ T cells was found in MSC-treated animals. In athymic rats, infiltration of neutrophils and macrophages was strong, but it occurred later than that in immunocompetent rats. While bone volume fraction significantly increased with time (P < .001), no difference was found between MSC-treated and control groups. CONCLUSIONS: Even in hosts with deficient T-cell immunity, xenogeneic BM-MSC transplantation into mandibular critical-sized defects still faces challenges from host innate immunity, which compromises their regenerative efficacy.

The Effect of Parathyroid Hormone Analogues When Added to Mineralized Bone Xenografts.

Implants can be a treatment option when there is sufficient quantity and quality of bone to provide support for long-term success. In the reconstruction of defects, autogenous bone remains the gold standard for its osteogenic and compatibility properties. However, the disadvantage of secondary surgery and the associated donor site morbidity prompts researchers to develop the ideal bone substitute for optimum bone reconstruction. Parathyroid hormone (PTH1-34) has provided a new option for improvement in bone regeneration. This study used a pig model to evaluate the effectiveness of parathyroid hormone when added to a xenograft, Bio-Oss, in reconstructing mandible defects. Six domestic pigs were used to create 3 posterior mandibular defects measuring 2 × 1-cm bilaterally with a total of 36 defects to simulate tooth extraction sites in humans. The defects were grafted in random order and divided into 3 groups as follows: control (no graft), Bio-Oss without PTH, and Bio-Oss with PTH. Defects were assessed with cone beam computerized tomography (CBCT), micro computerized tomography (microCT), nanoindentation, and histology. Results showed that adding PTH1-34 significantly enhanced the graft construct. CBCT showed a significant increase in the degree of bone mineralization. Nanoindentation showed increased hardness of regenerated bone and accelerated bone mineralization with PTH. MicroCT analysis revealed a trend toward higher bone regeneration and mineralization. The histological analysis showed a positive trend of the increase in cortical bone thickness and mineral apposition rate. In conclusion, the local addition of PTH1-34 to a xenograft has shown promising results to enhance bone regeneration in the reconstruction of mandibular defects.

Enhance Mandibular Symphyseal Surface Bone Growth with Autologous Mesenchymal Stem Cell Sheets: An Animal Study.

INTRODUCTION: The size and shape of the chin strongly influence facial profile and harmony. The current correction of chin deficiency mostly relies on genioplasty surgery involving osteotomy. To avoid osteotomy, one possible alternative is to enhance bone growth at the mental protuberance area with cell sheet transplantation. This study was undertaken to evaluate the efficacy of this approach in a pig model. MATERIALS AND METHODS: Five 4-month-old pigs were included for mandibular bone marrow aspiration and MSC isolation. Triple-layer MSC sheets were then fabricated and utilized using culture-expanded MSCs. Four weeks after bone marrow aspiration, subperiosteal pockets were created on the labial symphyseal surface, followed by transplantation of autogenous MSC sheets to one randomly chosen side with the other side (control) receiving no transplantation. Six weeks after the surgery, the pigs were euthanized and the specimens from both sides were collected for computed tomography (CT) and histological and immunohistochemical analysis. Measurements between the experimental and control sides were compared using paired t tests. RESULTS: MSC sheet fabrication and transplantation were reliably conducted. The labial cortical bone thickness increased significantly with MSC sheet transplantation by an average of 2 mm (p = 0.0001). The average measurements of mineral apposition rate and cell proliferation at the cell sheet side tended to be higher than the control side although the differences did not reach statistical significance (p = 0.1-0.2). Tissue mineral density measurements from CT images and bone volume fraction (BV/TV) measurements from histologic images were identical between the two sides (p > 0.5). CONCLUSION: These data provide a proof of concept that autologous MSC sheets may be transplanted to the subperiosteal region of the mandibular symphysis to stimulate local surface bone growth. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Macrophages mediate corticotomy-accelerated orthodontic tooth movement.

Clinical evidence has suggested that surgical corticotomy of the alveolar bone can accelerate local orthodontic tooth movement (OTM), but the underlying cell and molecular mechanisms remain largely unclear. The present study examined the role of macrophages played in corticotomy-assisted OTM. Orthodontic nickel-titanium springs were applied to the left maxillary first molars of rats or mice to induce OTM with or without corticotomy. Corticotomy enhanced OTM distance by accelerating movement through induction of local osteoclastogenesis and macrophage infiltration during OTM. Further analysis showed that macrophages were polarized toward an M1-like phenotype immediately after corticotomy and then switched to an M2-like phenotype during OTM. The microenvironment of corticotomy induced macrophage infiltration and polarization through the production of TNF-α. More importantly, the amount of OTM induced by corticotomy was significantly decreased after mice were depleted of monocyte/macrophages by injection of liposome-encapsulated clodronate. Further experiments by incubating cultured macrophages with fresh tissue suspension obtained from post-corticotomy gingiva switched the cells to an M1 phenotype through activation of the nuclear factor-κB (NF-κB) signaling pathway, and to an M2 phenotype through activation of the JAK/STAT3 signaling pathway. Our results suggest that corticotomy induces macrophage polarization first by activating the NF-κB signaling pathway and later by activating the JAK/STAT3 signaling pathway, and that these processes contribute to OTM by triggering production of inflammatory cytokines and osteoclastogenesis.

The usefulness of cone-beam computed tomography gray values for alveolar bone linear measurements.

OBJECTIVES: To test a proof-of-concept that the accuracy and reliability of alveolar bone height measurements from orthodontic grade (large field-of-view [FOV], large voxel-size) cone-beam computed tomography (CBCT) images may be improved by using pixel gray values. MATERIALS AND METHODS: Twenty fresh cadaver pig heads underwent CBCT scans (17 × 23 cm FOV, 0.4-mm voxel size). Buccal alveolar bone heights of maxillary first molars were measured using the conventional vision-based (VB) and the proposed gray value-assisted (GVA) methods. The GVA methods entailed localization of landmarks through observation of gray value pattern changes across tissue boundaries followed by mathematical calculation of distances between landmark pixels. Interrater reliability and accuracy of CBCT measurements made by all methods were statistically analyzed by comparing with physical measurements (gold standards). RESULTS: The interrater reliability of CBCT measurements made by GVA methods was comparable to physical measurements but higher than those made by the VB method. The GVA (bend-down pattern) method yielded average measurements similar to physical measurements, while those obtained by the VB and the GVA (straight pattern) methods were significantly larger (repeated measures analysis of variance, P < .001). The GVA (bend-down pattern) method also produced significantly more measurements within one voxel size of physical measurements than did the VB and GVA (straight pattern) methods (Chi-square tests, P < .017). CONCLUSIONS: These data confirm a concept that local gray value change patterns may be used to improve the accuracy and reliability of alveolar bone height measurement from large FOV and large voxel-size CBCT images.

Evaluation of objective structured clinical examination for advanced orthodontic education 12 years after introduction.

INTRODUCTION: Advanced education programs in orthodontics must ensure student competency in clinical skills. An objective structure clinical examination has been used in 1 program for over a decade. The results were analyzed cross-sectionally and longitudinally to provide insights regarding the achievement of competency, student growth, question difficulty, question discrimination, and question predictive ability. METHODS: In this study, we analyzed 218 (82 first-year, 68 second-year, and 68 third-year classes) scores of each station from 85 orthodontic students. The grades originated from 13 stations and were collected anonymously for 12 consecutive years during the first 2 decades of the 2000s. The stations tested knowledge and skills regarding dental relationships, analyzing a cephalometric tracing, performing a diagnostic skill, identifying cephalometric points, bracket placement, placing first-order and second-order bends, forming a loop, placing accentuated third-order bends, identifying problems and planning mixed dentition treatment, identifying problems and planning adolescent dentition treatment, identifying problems and planning nongrowing skeletal treatment, superimposing cephalometric tracings, and interpreting cephalometric superimpositions. Results were evaluated using multivariate analysis of variance, chi-square tests, and latent growth analysis. RESULTS: The multivariate analysis of variance showed that all stations except 3 (analyzing a cephalometric tracing, forming a loop, and identifying cephalometric points) had significantly lower mean scores for the first-year student class than the second- and third-year classes (P <0.028); scores between the second- and third-year student classes were not significantly different (P >0.108). The chi-square analysis of the distribution of the number of noncompetent item responses decreased from the first to the second years (P <0.0003), from the second to the third years (P <0.0042), and from the first to the third years (P <0.00003). The latent growth analysis showed a wide range of difficulty and discrimination between questions. It also showed continuous growth for some areas and the ability of 6 questions to predict competency at greater than the 80% level. CONCLUSIONS: Objective structure clinical examinations can provide a method of evaluating student performance and curriculum impact over time, but cross-sectional and longitudinal analyses of the results may not be complementary. Significant learning appears to occur during all years of a 3-year program. Valuable questions were both easy and difficult, discriminating and not discriminating, and came from all domains: diagnostic, technical, and evaluation/synthesis.

Similarities and differences between porcine mandibular and limb bone marrow mesenchymal stem cells.

OBJECTIVE: Research has shown promise of using bone marrow mesenchymal stem cells (BMSCs) for craniofacial bone regeneration; yet little is known about the differences of BMSCs from limb and craniofacial bones. This study compared pig mandibular and tibia BMSCs for their in vitro proliferation, osteogenic differentiation properties and gene expression. DESIGN: Bone marrow was aspirated from the tibia and mandible of 3-4 month-old pigs (n=4), followed by BMSC isolation, culture-expansion and characterization by flow cytometry. Proliferation rates were assessed using population doubling times. Osteogenic differentiation was evaluated by alkaline phosphatase activity. Affymetrix porcine microarray was used to compare gene expressions of tibial and mandibular BMSCs, followed by real-time RT-PCR evaluation of certain genes. RESULTS: Our results showed that BMSCs from both locations expressed MSC markers but not hematopoietic markers. The proliferation and osteogenic differentiation potential of mandibular BMSCs were significantly stronger than those of tibial BMSCs. Microarray analysis identified 404 highly abundant genes, out of which 334 genes were matched between the two locations and annotated into the same functional groups including osteogenesis and angiogenesis, while 70 genes were mismatched and annotated into different functional groups. In addition, 48 genes were differentially expressed by at least 1.5-fold difference between the two locations, including higher expression of cranial neural crest-related gene BMP-4 in mandibular BMSCs, which was confirmed by real-time RT-PCR. CONCLUSIONS: Altogether, these data indicate that despite strong similarities in gene expression between mandibular and tibial BMSCs, mandibular BMSCs express some genes differently than tibial BMSCs and have a phenotypic profile that may make them advantageous for craniofacial bone regeneration.

Comparison of cone-beam computed tomography with multislice computed tomography in detection of small osseous condylar defects.

INTRODUCTION: Previous studies have indicated that orthodontic-grade cone-beam computed tomography (CBCT) images are limited when displaying small defects at the mandibular condyles for diagnosis. In this study, we investigated whether this limitation was inherent to CBCT by comparing CBCT with multislice computed tomography (CT), and whether image segmentation and color mapping could overcome this limitation. METHODS: Nine fresh pig heads (18 condyles, 36 medial and lateral condylar regions) were used. Small osseous defects (diameter and depth, 1.5 mm) were created at the medial and lateral regions of the condyles shown by gutta percha markers. After the overlying soft tissues were restored, the pig heads underwent orthodontic-grade CBCT scans (0.4-mm voxel size; i-CAT; Imaging Sciences International, Hatfield, Pa) and medical-grade CT scans (0.625-mm voxel size; LightSpeed; GE, Little Chalfont, Buckinghamshire, United Kingdom). Subsequently, 2 calibrated and blinded raters diagnosed the defect numbers in each condylar region from CBCT and CT images using Dolphin 3D software (Patterson Supply, St Paul, Minn) without image segmentation, and then 1 week later with the proprietary image segmentation and color mapping tools of Dolphin 3D. Condylar polyvinyl siloxane impressions were collected and evaluated by the same raters to obtain physical diagnoses. Rediagnoses were made on randomly selected subsamples to assess reliability. Using the physical diagnoses as references, the accuracy of imaging diagnosis was assessed and statistically compared among the varied imaging and analysis methods. RESULTS: Image diagnoses of all imaging and analysis methods showed good or excellent intrarater and interrater reliability values, except for those of the segmented CBCT images, which were substantially lower. The numbers of overdiagnoses and underdiagnoses per condylar region were not significantly different among the varied imaging and analysis methods (Wilcoxon tests, P >0.05), but classification functions demonstrated substantially lower sensitivity and accuracy with CBCT than with CT. Logistic regression also showed that CT had a significantly higher probability (odds ratio, 2.4) than CBCT in reaching the correct diagnosis, whereas use of the image segmentation and color mapping tool proprietary to Dolphin 3D did not improve the diagnostic accuracy from CBCT images. CONCLUSIONS: Even at a lower voxel size than medical CT images, orthodontic-grade CBCT images of mandibular condyles may be inherently less reliable and less accurate for the diagnosis of small condylar defects.

Reconstructing jaw defects with MSCs and PLGA-encapsulated growth factors.

Cell and growth factor-based tissue engineering has shown great potentials for skeletal regeneration. This study tested its feasibility in reconstructing large mandibular defects and compared the efficacy of varied construction materials and sealing methods. Bilateral mandibular critical-size (5-cm(3)) defects were created on six 4-month-old domestic pigs, and grafted with ß-tricalcium phosphate (ßTCP) only (Group-A), ßTCP with autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) (Group-B), and ßTCP with BM-MSCs and biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres containing bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) (Group-C). The buccal sides of Groups-B/-C were either sealed by fibrin sealant or by a biodegradable PLGA barrier membrane before soft-tissue closure. Computed tomography (CT), microCT and histology analyses were performed 12 weeks postoperatively. In vitro data demonstrated that BM-MSCs, with MSC properties confirmed, remained vital after integration with ßTCP; and PLGA microspheres exhibited an initial burst followed by slow and continuous release of growth factors over a period of 28 days. In vivo data demonstrated that Group-B/-C sites had significantly greater gap obliteration, higher tissue mineral densities and more residual ßTCP granules (p<0.05, Kruskal-Wallis tests). Qualitatively, Group-B/-C defect sites had started remodeling while Group-A sites were mainly forming new bone to bridge the gaps. Furthermore, ßTCP degradation was not mediated by macrophages or osteoclasts, and was significantly slowed down by sealing the defects with barrier membrane. Combined, these data present a promising formulation composed of ßTCP granules, autologous MSCs, controlled-release growth factors and biodegradable PLGA barrier membrane for the reconstruction of critical-size mandibular defects.

Mandibular bone mineral density variation in three West African Cercopithecoid monkey species: associations with diet and feeding behavior.

OBJECTIVE: Procolobus badius, Colobus polykomos, and Cercocebus atys are three West African primate species known to have distinctive feeding behaviors. Our objectives were (1) to test whether intra-taxon variation in bone mineral content exists between anterior and posterior regions of the mandible and (2) to determine if interspecific differences are interpretable via feeding and dietary idiosyncracies among the three taxa. DESIGN: Twenty-one mandibles from naturally deceased C. polykomos (n=7), P. badius (n=9), and C. atys (n=5) were scanned using cone beam computerized tomography. Alveolar bone (AB) and basal cortical bone (CB) of incisor (I1) and second molar (M2) regions were digitally isolated. Degree of bone mineralization (DBM) distribution was obtained using histograms of CT attenuation values. Mean, standard deviation (SD), the 5th (Low5) and the 95th (High5) percentiles of the DBM histogram were compared between the jaw regions in species. RESULTS: The mean and Low5 of DBM were significantly lower for AB than CB of all species (p<0.001). The AB DBM parameters were not significantly different between I1 and M2 of all species (p>0.056) except the mean of C. polykomos (p<0.05). The mean, SD, High5 of CB DBM at M2 of C. atys was significantly higher than those of C. polykomos and P. badius (p<0.006). CONCLUSIONS: The durophagous C. atys had higher CB DBM value at the M2 region than C. polykomos and P. badius, which supports the hypothesis that materially stiffer mandibular bone in C. atys can develop in response to the generation of high bite forces during hard object feeding.

[Maxillary canine impaction increases root resorption risk of adjacent teeth: A problem of physical proximity]. / La canine maxillaire incluse augmente le risque de résorption radiculaire des dents adjacentes : un problème de proximité anatomique∗.

INTRODUCTION: Our objectives were to investigate the prevalence, resorption location and extent, and potential risk factors for impacted canine-associated root resorption (ICARR) in Chinese patients, who, unlike white patients, have predominantly buccal maxillary canine impactions. METHODS: Pretreatment cone-beam computed tomography scans of 170 Chinese subjects (ages, 12-30 years; mean, 14.5 years) with impacted maxillary canines (101 buccal and 69 palatal impactions) and 170 age- and sex-matched subjects without impactions were used. All cone-beam computed tomography records were evaluated in software programs by 1 rater. The prevalence, location, and extent of ICARR at the maxillary lateral incisor, central incisor, and first premolar were analyzed. To identify risk factors for ICARR, the subjects with impacted canine were divided into 2 groups (with and without root resorption). Measurements of 10 variables were individually compared between the groups and then tested together by using binary logistic regressions for each tooth. RESULTS: Compared with the control subjects and the side of nonimpaction, root resorption was significantly more prevalent in the canine-impaction subjects and the side of impaction (P\0.01), with overall prevalence rates of 27%, 18% and 10% at the maxillary lateral incisor, the central incisor, and the first premolar, respectively. Predominantly affecting the apical third of all teeth, ICARR, if present, reached the pulp of the maxillary lateral incisor, the central incisor, and the first premolar at rates of 36%, 57%, and 0%, respectively. Individually, variables reflecting the proximity to the impacted maxillary canine had different measurements (P\0.05) between the impaction sites (maxillary quadrants) with and without root resorption for each tooth, whereas the canine development stage factor was only significant for the maxillary central and lateral incisors. No significant difference of ICARR prevalence was found between subjects with buccal and palatal impactions. Combined, the contact relationship was the dominant predictor for ICARR at all teeth, with "in contact" (\1 mm separation) having the largest and most significant increase of root resorption likelihood compared with "out of contact" ($1 mm separation); odds ratios were 9.9, 3.7 and 5.9 for the maxillary lateral incisor, the central incisor, and the first premolar, respectively. CONCLUSIONS: Maxillary canine impaction increases the risk of root resorption at adjacent teeth (incisors and first premolars). Physical proximity (\1 mm) between the impacted canine and an adjacent root is the most important predictor for root resorption, and this characteristic is largely similar in Chinese patients to that in white people.

Establishing a critical-size mandibular defect model in growing pigs: characterization of spontaneous healing.

PURPOSE: A large animal model is desired for preclinical studies aimed at reconstructing severe mandibular skeletal defects using tissue engineering techniques. To identify the size and location requirements for a mandibular critical-size bone defect in growing pigs, the present study investigated the spontaneous healing of surgically created mandibular defects. MATERIALS AND METHODS: Six 4-month-old domestic pigs were used. In pigs 1 and 2, a 3-, 5-, or 7-cm(3) subperiosteal mandibular defect was created. In pigs 3 to 6, 3- to 5-cm(3) bilateral defects were randomly created at the anterior (apical to the molars) and posterior (mandibular angle) mandibular regions. Spontaneous healing of these defects was assessed by serial computed tomography scans (postoperative week 1, 6, and 12) and histologic analyses. RESULTS: In pigs 1 and 2, regardless of defect size, the anterior, but not posterior, defects had largely healed. Systematic analyses of pigs 3 to 6 revealed, first, the extent of defect regeneration from spontaneous healing was significantly less in the posterior than in the anterior defects, with about two thirds and one third of the original defect volume remaining, respectively. Second, histologically, the posterior defects had considerably less regeneration and more evident tapering of the new bone than did the anterior defects. Finally, the buccal periosteum had completely regenerated in the anterior defects, but had only partially done so in the posterior defects. Also, the buccal surface contour was moderately concave in the anterior defects, but it was severely concave in the posterior defects. CONCLUSIONS: Despite robust spontaneous healing of mandibular defects in growing pigs, 5-cm(3) defects in the mandibular angle region without buccal periosteum would be a reasonable critical-size defect model relevant to mandibular defects in adolescent humans.

Evaluation of cone-beam computed tomography in the diagnosis of simulated small osseous defects in the mandibular condyle.

INTRODUCTION: In this study, we investigated the impact of defect size and scan voxel size on the accuracy of cone-beam computed tomography (CBCT) diagnoses of simulated condylar defects and assessed the value of orthodontic CBCT images typically scanned at lower settings (0.4-mm voxel size and full-size field of view) in diagnosing condylar erosion defects. METHODS: Cylindrical holes simulating condylar defects with varied diameters (≤2, 2-3, and >3 mm) and depths (≤2 and >2 mm) were created in 22 fresh pig mandibular condyles, with defect number and size per condyle and quadrant randomly determined. With the soft tissues repositioned, 2 CBCT scans (voxel sizes, 0.4 and 0.2 mm) of the pig heads were obtained from an i-CAT unit (Imaging Science International, Hatfield, Pa). Reconstructed CBCT data were analyzed independently by 2 calibrated, blinded raters using Dolphin-3D (Dolphin Imaging and Management Solutions, Chatsworth, Calif) for defect identification and localization and defect diameter and depth measurements, which were compared with physical diagnoses obtained from polyvinyl siloxane impressions. RESULTS: Identification and localization of simulated defects demonstrated moderate interrater reliability and excellent specificity and sensitivity, except for extremely small defects (both diameter and depth ≤2 mm) viewed with 0.4-mm scans, which had a significantly lower sensitivity (67.3%). Geometric measurements of simulated defects demonstrated good but not excellent interrater reliability and submillimeter inaccuracy for all defects. Receiver operating characteristic analyses demonstrated that the overall accuracy of diagnosing simulated condylar defects based on CBCT geometric measurements was fair and good for the 0.4-mm and 0.2-mm voxel-size scans, respectively. With the prevalence of condylar erosion defects in the patients considered, the positive predictive values of diagnoses based on 0.5-mm size (diameter or depth) cutoff points were near 15% and 50% for asymptomatic and symptomatic temporomandibular joints, respectively; the negative predictive values were near 95% and 90%, respectively. CONCLUSIONS: When using orthodontic CBCT images for diagnosing condylar osseous defects, extremely small (<2 mm) defects can be difficult to detect; caution is also needed for the diagnostic accuracy of positive diagnoses, especially those from asymptomatic temporomandibular joints.

Scaffold-based delivery of autologous mesenchymal stem cells for mandibular distraction osteogenesis: preliminary studies in a porcine model.

PURPOSE: Bone regeneration through distraction osteogenesis (DO) is promising but remarkably slow. To accelerate it, autologous mesenchymal stem cells have been directly injected to the distraction site in a few recent studies. Compared to direct injection, a scaffold-based method can provide earlier cell delivery with potentially better controlled cell distribution and retention. This pilot project investigated a scaffold-based cell-delivery approach in a porcine mandibular DO model. MATERIALS AND METHODS: Eleven adolescent domestic pigs were used for two major sets of studies. The in-vitro set established methodologies to: aspirate bone marrow from the tibia; isolate, characterize and expand bone marrow-derived mesenchymal stem cells (BM-MSCs); enhance BM-MSC osteogenic differentiation using FGF-2; and confirm cell integration with a gelatin-based Gelfoam scaffold. The in-vivo set transplanted autologous stem cells into the mandibular distraction sites using Gelfoam scaffolds; completed a standard DO-course and assessed bone regeneration by macroscopic, radiographic and histological methods. Repeated-measure ANOVAs and t-tests were used for statistical analyses. RESULTS: From aspirated bone marrow, multi-potent, heterogeneous BM-MSCs purified from hematopoietic stem cell contamination were obtained. FGF-2 significantly enhanced pig BM-MSC osteogenic differentiation and proliferation, with 5 ng/ml determined as the optimal dosage. Pig BM-MSCs integrated readily with Gelfoam and maintained viability and proliferative ability. After integration with Gelfoam scaffolds, 2.4-5.8×10(7) autologous BM-MSCs (undifferentiated or differentiated) were transplanted to each experimental DO site. Among 8 evaluable DO sites included in the final analyses, the experimental DO sites demonstrated less interfragmentary mobility, more advanced gap obliteration, higher mineral content and faster mineral apposition than the control sites, and all transplanted scaffolds were completely degraded. CONCLUSION: It is technically feasible and biologically sound to deliver autologous BM-MSCs to the distraction site immediately after osteotomy using a Gelfoam scaffold to enhance mandibular DO.

Etiologic factors for buccal and palatal maxillary canine impaction: a perspective based on cone-beam computed tomography analyses.

INTRODUCTION: The aim of this research was to identify the etiologic factors associated with palatally impacted canines and buccally impacted canines in a Chinese population by using the cone-beam computed tomography technique. METHODS: Pretreatment cone-beam computed tomography scans of 170 Chinese subjects with impacted maxillary canines and 170 age- and sex-matched subjects without impaction were used. Impacted canine subjects were divided into 2 groups: those with palatally impacted canines and those with buccally impacted canines. One rater analyzed the cone-beam computed tomography data for qualitative and quantitative variables of the teeth, dental arch, and skeletal components. The measurements were compared by using analytical statistical methods. RESULTS: The mesiodistal dimension of the lateral incisor was significantly smaller in the palatally impacted canine group than in the other group (by an average of 0.4-0.5 mm; analysis of variance [ANOVA], P <0.001). Both anterior maxillary dental (interpremolar) width and skeletal width (interjugal points) in the buccally impacted canine group were significantly smaller than in the palatally impacted canine and control groups (ANOVA, P <0.001), whereas the intermolar widths and posterior mandibular widths were similar among the groups. The groups with palatally impacted or buccally impacted canines had significantly increased prevalence values of peg-shaped lateral incisors and incisor impaction, respectively (chi-square or Fisher exact tests, P <0.001). After excluding subjects who also had lateral incisor anomalies, the prevalence values of supernumerary teeth, missing premolars, or third molars combined were not different among the impaction and control groups. The average mesiodistal location of the canine cusp tip was significantly different between the buccally impacted canines and the palatally impacted canines groups; it was distal and mesial to the lateral incisor long axis, respectively. CONCLUSIONS: In Chinese subjects, buccal canine impaction is mostly associated with anterior transverse (dental and skeletal) deficiency and incisor impaction, whereas palatal impaction is mostly associated with small or missing lateral incisors, consistent with the guidance theory. Likely, preimpaction migrations of the canines are mainly buccal for buccal impactions and excessively mesiopalatal for palatal impactions.

Factors affecting the accuracy of buccal alveolar bone height measurements from cone-beam computed tomography images.

INTRODUCTION: The reasons for inaccuracies in alveolar bone measurement from cone-beam computed tomography (CBCT) images might be multifactorial. In this study, we investigated the impact of software, the presence or absence of soft tissues, the voxel size of the scan, and the regions in the jaws on buccal alveolar bone height measurements in pigs at an age equivalent to human adolescents. METHODS: Marker holes, apical to the maxillary and mandibular molar roots, and mesiodistal molar occlusal reference grooves were created in 6 fresh pig heads (12 for each jaw), followed by CBCT scans at 0.4-mm and 0.2-mm voxel sizes under soft-tissue presence and soft-tissue absence conditions. Subsequently, buccolingual sections bisecting the marker holes were cut, from which the physical alveolar bone height and thickness were measured. One blinded rater, using Dolphin (version 11.5 Premium; Dolphin Imaging, Chatsworth, Calif) and OsiriX (version 3.9; www.osirix-viewer.com) software, independently collected alveolar bone height measurements from the CBCT images. Differences between the CBCT and the physical measurements were calculated. The mean differences and the limit of agreement (LOA, ±1.96 SD) for every jaw, voxel-size, soft-tissue, and software condition were depicted. Each measurement was then assessed for clinical inaccuracy by using 2 levels of criteria (absolute differences between CBCT and physical measurements ≥1 mm, or absolute differences between CBCT and physical measurements ≥0.5 mm), and the interactions between soft-tissue and voxel-size factors for every jaw and software condition were assessed by chi-square tests. RESULTS: Overall, the mean differences between the CBCT and the physical measurements for every jaw, voxel-size, soft-tissue, and software condition were near 0. With all other conditions kept equal, the accuracy of the maxillary CBCT measurements was inferior (larger limit of agreement ranges and higher frequencies of clinical inaccuracy) to the mandibular measurements. The physical thickness of the maxillary alveolar crestal bone was less than 1 mm and significantly thinner than the mandibular counterparts. For every jaw and software condition, the accuracy of measurements from the 0.2-mm soft-tissue presence CBCT images was consistently superior (smaller limit of agreement ranges and lower frequencies of clinical inaccuracy) to those from the 0.4-mm soft-tissue presence, the 0.4-mm soft-tissue absence, and the 0.2-mm soft-tissue absence images; all showed similar accuracies. Qualitatively, the soft-tissue absence images demonstrated much brighter enamel and alveolar bone surface contours than did the soft-tissue presence images. CONCLUSIONS: At an adolescent age, the buccal alveolar bone height measured from the maxillary molar region based on 0.4-mm voxel-size CBCT images can have relatively large and frequently inaccurate measurements, possibly due to its thinness. By using 0.2-mm voxel-size scans, measurement accuracy might be improved, but only when the overlying facial and gingival tissues are kept intact.